The spliceosome is a colossal ribonucleoprotein assembly, built from five small nuclear RNAs and well over a hundred proteins. It assembles anew on every single intron in every pre-messenger RNA molecule, and once it has excised the intron as a looped structure called a lariat, the ligated mRNA is released. But the excised intron-lariat stays wedged inside the RNA-based active site of the machine, forming a stable complex known as the intron-lariat spliceosome. This state is a dead end. To sustain the relentless pace of splicing in a growing cell, the intron-lariat spliceosome must be dismantled so that its proteins and small nuclear RNAs can be reused, and the trapped intron must be ejected, straightened out at its branch point, and ultimately degraded. These combined events constitute spliceosome termination, and until now the molecular details of how they unfold have been largely unknown.

A team led by researchers at the Research Institute of Molecular Pathology in Vienna, working with colleagues in the Netherlands and Spain, set out to catch the spliceosome in the act of terminating. Their strategy combined cryo-electron microscopy of spliceosomes purified directly from human cells with biochemistry, RNA sequencing and genetic experiments. By tagging the proteins DHX35 and YJU2B in human K562 cells and purifying the spliceosome complexes associated with them, the researchers obtained two distinct molecular snapshots. The first, resolved at a remarkable 2.4 angstrom resolution, captured a state they named the ILS-AQR complex. The second, at 3.2 angstroms, revealed an entirely new intermediate that they called the debranched intron spliceosome, or DIS. Together, these structures trace the sequential stages through which the spliceosome passes as it winds down its work.

The ILS-AQR structure revealed several surprises. The team identified a previously uncharacterized termination factor, YJU2B, bound to the spliceosome alongside the known termination factors TFIP11, C19L1, C19L2 and the RNA helicase DHX15. More strikingly, they found that the RNA helicase Aquarius, a protein already known for its role in spliceosome activation, was gripping the circular portion of the intron-lariat RNA in its active site. Aquarius belongs to a family of helicases that move along single-stranded RNA in a defined direction, and the structure showed it poised to pull on the intron-lariat branch point adenosine, the chemical knot that holds the lariat loop together. The researchers propose that Aquarius, guided by the RNA-binding protein PPIE, tugs the branch point out of the spliceosomal RNA network, while DHX15 simultaneously unwinds a different RNA element on the opposite side. Two RNAs pulled in opposite directions, the authors suggest, begin to unravel the intricate RNA architecture that holds the spliceosome together.

Extracting the branch point serves a second critical purpose: it exposes the knot so that it can be cut open. The enzyme responsible is DBR1, a debranching enzyme whose action is essential for intron turnover and for maintaining the balance of RNA in the cell nucleus. The new study provides the first molecular evidence that debranching happens directly on the spliceosome. Through a combination of proximity labelling, protein interaction predictions and biochemical validation, the researchers showed that DBR1 is tethered to the spliceosome through two conserved peptide segments in its tail. One of these peptides binds the termination factor C19L1, anchoring the catalytic domain of DBR1 within reach of the extracted branch point. Experiments in human cells confirmed the biological importance of this connection: DBR1 lacking the peptide could not rescue the growth defect caused by acute depletion of the endogenous enzyme, whereas the full-length protein could.

Once the branch point has been cut and the early termination factors have been displaced, the spliceosome enters the newly discovered DIS state. In this complex, the RNA network is almost completely dismantled. The U2 snRNP, the ESS2 protein and all six ILS-specific termination factors are gone, and the excised intron, now linearized, remains attached only through a short duplex between the U6 small nuclear RNA and the 5-prime splice site. RNA sequencing of the introns associated with each complex confirmed that the vast majority of DIS-bound introns had indeed been debranched, and that nearly all introns found in the ILS-AQR state were also detected in the DIS, indicating that passage through these two states is the predominant termination pathway for human introns.

The final blow is delivered by the RNA helicase DHX35, recruited to the DIS together with its cofactors GPATCH1 and WDR83. The structure shows DHX35 anchored on the spliceosome through extensive contacts with GPATCH1, which itself winds around the PRP8 protein at the heart of the machine. The U6 snRNA regions just downstream of the splice-site pairing are positioned to dock into the DHX35 active site, and the authors propose that DHX35 translocates along U6 snRNA, unwinding the remaining helical turn of the U6-intron duplex and ejecting the debranched intron for decay. In support of this model, purified DIS complexes immobilized on beads released their U5 snRNP and associated protein complexes upon addition of ATP, but only when DHX35 was catalytically competent. A mutant version of DHX35 unable to hydrolyse ATP bound the spliceosome normally yet failed to trigger disassembly, demonstrating that the helicase actively drives the final separation.

The study also illuminates how the cell deals with spliceosomes that go wrong. Splicing is not always successful, and defective complexes assembled on aberrant introns must be recognized and dismantled through a quality-control pathway. By revising an existing structure of a defective spliceosome from fission yeast, the researchers identified two additional factors, the YJU2B orthologue Saf4 and an uncharacterized protein called LENG1. LENG1, a paralogue of the essential branching factor CWC25, appears to partner with YJU2B specifically in defective complexes, where it helps guide the DHX35-GPATCH1-WDR83 machinery to the stalled spliceosome. The same helicases, DHX15 and DHX35, therefore serve both routine termination and quality control, but in regular termination they act in two sequential states, whereas in defective complexes they can be deployed simultaneously for a single-step disassembly.

The significance of this work extends beyond the mechanics of one molecular machine. Errors in splicing are implicated in a wide range of human diseases, including cancers driven by mutations in the splicing factor SF3B1, and the factors identified here, several of which rank among each other’s strongest genetic dependencies in human cell screens, may represent new points of vulnerability. By revealing how three RNA helicases, Aquarius, DHX15 and DHX35, orchestrate the gradual dismantling of the spliceosomal RNA network, coupling intron debranching and ejection to machine disassembly, the study closes a long-standing gap in our understanding of gene expression. Every protein-coding message in the human body depends on this final act of molecular housekeeping, and it has now, at last, been caught on camera.

Subject of Research: Structural mechanism of human spliceosome termination and intron-lariat debranching

Article Title: Mechanism of spliceosome termination

Article References: Boreikaite, V., Faraway, R., Vorländer, M. K., Phillips, A. W., Opitz, L., Wanke, M., Yakoub, G., Raffl, G., Fin, L., González-Prieto, R., Luijsterburg, M. S., Ameres, S. L., & Plaschka, C. (2026). Mechanism of spliceosome termination. Nature. https://doi.org/10.1038/s41586-026-11101-6

Image Credits: AI Generated

DOI: 10.1038/s41586-026-11101-6

Keywords: spliceosome, pre-mRNA splicing, cryo-electron microscopy, intron lariat, DHX35, DHX15, Aquarius, DBR1, RNA helicase, spliceosome recycling, RNA quality control, gene expression

The research, led by Tülay Karakulak and Abdullah Kahraman of the Swiss Institute of Bioinformatics and their collaborators, including Holger Moch of the University Hospital Zurich and Christian von Mering of the University of Zurich, drew on an extraordinary wealth of data. The team analysed bulk RNA sequencing from 1,117 cancer patients with metastatic melanoma, ovarian cancer, or acute myeloid leukemia (AML), combining samples from the Tumor Profiler (TuPro) Project, a multi-omics clinical study based in Zurich, with data from The Cancer Genome Atlas (TCGA). To determine what a ‘normal’ splicing pattern looks like, they compared the tumour samples against 818 healthy tissue samples from the Genotype-Tissue Expression (GTEx) project, using skin, ovary, and blood samples as the appropriate reference tissues. For each gene in each sample, the researchers identified the Most Dominant Transcript, the isoform that is expressed at the highest level, and then looked for cases where the dominant isoform in a cancer sample differed from the dominant isoform in healthy tissue. These cancer-specific dominant transcripts, abbreviated cMDTs, are the molecular fingerprints of isoform switching.

The scale of what they found is striking. Across the three cancer types, the team identified 6,114 unique cancer-associated dominant transcripts arising from 4,151 genes. Of these, 1,707 encode transmembrane proteins, a particularly important class because many diagnostic assays and targeted therapies act on proteins embedded in the cell membrane. Most of these switches were rare, patient-specific events: 41 percent of the cMDTs were detected in only a single sample, and the majority appeared in fewer than 10 percent of samples within a cohort. Yet 526 of the switches were found in more than 30 percent of samples in at least one cancer cohort, and 131 of those involved transmembrane proteins. Metastatic epithelial ovarian cancer and metastatic melanoma showed the highest numbers of switching events, while AML showed the fewest, confirming earlier observations that splicing aberrations differ markedly between cancer types. The researchers also found that samples in which a spliceosome gene, encoding a component of the splicing machinery itself, had undergone a dominant-transcript switch carried significantly more cMDTs than other samples, whereas mutations in spliceosome genes without a switch did not produce the same effect. This suggests that functional disruption of the splicing machinery, rather than mutation alone, drives large-scale splicing chaos in tumours.

Among the most frequent switches was one involving the cytoskeletal gene ADD3, or adducin 3. In ovarian cancer, a longer isoform of ADD3 that includes an extra exon was the dominant transcript in 82 percent of metastatic TuPro samples and 91.3 percent of TCGA samples. Previous work in lung cancer has shown that inclusion of this exon, exon 14, is associated with poor prognosis, likely because downregulation of the RNA-binding protein QKI-5, which normally prevents that exon from being included, promotes cell proliferation. Another notable example in ovarian cancer concerned SLC44A2, the gene encoding the choline transporter-like protein CTL2. Healthy ovarian tissue predominantly produces a 704-amino-acid version called CTL2-P1, whereas ovarian tumours frequently switch to a slightly longer variant, CTL2-P2, which uses a different starting exon and carries a distinct N-terminal region. Crucially, only the CTL2-P2 variant has detectable choline transport activity. Because aberrant choline metabolism is known to fuel cancer progression, targeting this isoform switch could offer a therapeutic angle in ovarian cancer, and the team noted that nearly 8 percent of TCGA ovarian samples also carry amplifications of the SLC44A2 gene.

In melanoma, the spotlight fell on PDCD6, a gene involved in programmed cell death. The dominant isoform in healthy skin encodes a protein with five EF-hand domains, structural motifs that bind calcium and mediate interactions with other proteins. The cancer-specific isoform retains only two of these domains, which likely cripples its ability to interact with binding partners such as DAPk1, which promotes apoptosis, and VEGFR-2, through which PDCD6 inhibits angiogenesis. In other words, the tumour appears to be splicing away the very machinery that would help kill it. In AML, the team identified a switch to the longest isoform of USP34, a ubiquitin-specific peptidase whose overexpression has been linked to tumour growth in pancreatic cancer and laryngeal carcinoma. And in a striking ovarian cancer finding, the tumour suppressor TP53 itself showed isoform switching in 20 samples, with 18 samples expressing a 261-amino-acid variant known as Δ133p53α. This isoform lacks both transactivation domains, a proline-rich domain, and part of the DNA-binding domain, and according to the team’s interaction database it cannot bind critical partners including MDM2, MDM4, POLR2E, and EP300, fundamentally altering the behaviour of one of the most studied proteins in all of cancer biology.

Identifying these switches at the RNA level is one thing; proving that the altered proteins are actually made is another. To do this, the researchers turned to data-independent acquisition mass spectrometry from matched TuPro protein samples, developing a three-tiered evidence system. Class I evidence comes from peptides unique to the cancer-specific isoform, the strongest possible proof that the switched protein is translated. Class II evidence uses peptides found on the cancer isoform and other non-canonical isoforms but absent from the normal dominant transcript. Class III evidence, the weakest tier, relies on differential expression patterns of multiple peptides between samples with and without the switch. Together, these approaches validated 12.1 percent of the more than 33,000 identified cMDTs, one of the highest detection rates reported to date. The validated switches included the ADD3 long isoform, detected with a specific peptide in 45 percent of matched ovarian cancer proteomics samples, and a long isoform of ATP2B4, a calcium-transporting enzyme implicated in apoptotic resistance in pancreatic cancer, found in 77.5 percent of matched samples. Importantly, a search of normal ovary proteomics data in the PaxDB database found no trace of the ADD3 cancer-specific peptide, underscoring its potential as a tumour-specific marker.

Perhaps the most consequential part of the study concerns what these switched proteins can no longer do. The team built an updated version of their CanIsoNet database, mapping nearly 100,000 protein isoforms onto the latest STRING protein interaction network and the 3did database of domain-domain interactions. Among 1,652 cMDTs with domain interaction information, 906 had lost all interactions with their protein partners, while only 718 retained all of them. A vivid example is TRAPPC5, a subunit of a vesicle-transporting complex that shuttles cargo from the endoplasmic reticulum to the Golgi. In melanoma, a truncated 121-amino-acid isoform of TRAPPC5 was the dominant transcript in up to two-thirds of samples, compared with a 188-amino-acid version in healthy tissue, and the shortened protein loses every one of its native interaction partners, including clinically annotated proteins. High expression of this truncated isoform was associated with lower survival in TCGA data, whereas expression of the normal isoforms had no survival impact, marking it as a candidate biomarker for melanoma.

The implications for drug treatment may be even more significant. The researchers constructed a new database, called IsoDrug, that links protein isoforms to the small molecules and drugs that bind them, drawing on structural data from more than 8,600 entries in the Protein Data Bank. Of the 641 cMDTs with drug interaction information, whose canonical counterparts are targets of 166 drugs, 56 percent had lost the binding residues needed to interact with their potential drug targets. Among tyrosine kinase inhibitors, the workhorse drugs of precision oncology, the team found 15 cancer-specific isoforms whose canonical versions bind one of 11 TKI compounds. The most frequent was a 154-amino-acid isoform of PDGFRA, expressed predominantly in melanoma samples, which lacks the entire tyrosine kinase domain that the drug sunitinib targets. A similar case is EPHB4, a receptor overexpressed in ovarian cancer, whose cancer-specific isoform retains only the ligand-binding domain and has lost the complete kinase domain targeted by inhibitors. Patients whose tumours predominantly express these truncated isoforms would likely derive no benefit from the corresponding drugs, even if the gene itself appears amplified or mutated on standard genomic tests.

The authors are careful to note the limitations of their work. Many of the single-sample switches could reflect technical variability rather than true biology, and the short-read sequencing they used cannot capture full-length transcripts as precisely as emerging long-read methods would. They also defined cancer-specific switches strictly within each tissue context, meaning some of these isoforms may exist in other healthy tissues. Still, the path forward is clear: the team highlights isoform-specific peptides from ADD3, ATP2B4, and PARP14 as prime candidates for liquid biopsy tests that could detect cancer or guide therapy decisions from a simple blood sample, and they call for drug-screening experiments in patient-derived cell cultures to confirm the predicted losses of drug binding. What emerges from this study is a compelling message for oncology: reading a tumour’s genome is no longer enough. To understand what a cancer is truly capable of, and which drugs it will resist, clinicians and researchers must also read the tumour’s RNA, exon by exon, and ask not just which genes are active, but which versions of their proteins the cancer has chosen to build.

Subject of Research: Alternative splicing isoform switches and their effects on protein and drug interactions in melanoma, ovarian cancer, and acute myeloid leukemia

Article Title: Switches in alternatively spliced isoforms impact protein and drug interactions in melanoma, ovarian cancer, and acute myeloid leukemia

Article References: Karakulak, T., Tumor Profiler Consortium, Aebersold, R., Ak, M., Al-Quaddoomi, F. S., Albert, S. I., Albinus, J., Alborelli, I., Andani, S., Attinger, P.-O., Bacac, M., Baciu-Drăgan, M.-A., Baumhoer, D., Beck-Schimmer, B., Beerenwinkel, N., Beisel, C., Bernasconi, L., Bertolini, A., Bodenmiller, B., … Kahraman, A. (2026). Switches in alternatively spliced isoforms impact protein and drug interactions in melanoma, ovarian cancer, and acute myeloid leukemia. British Journal of Cancer. https://doi.org/10.1038/s41416-026-03638-0

Image Credits: AI Generated

DOI: 10.1038/s41416-026-03638-0

Keywords: alternative splicing, isoform switching, melanoma, ovarian cancer, acute myeloid leukemia, biomarkers, drug resistance, proteomics, spliceosome, TP53, PDGFRA, transmembrane proteins

Alternative splicing is the process by which a single gene produces multiple distinct messenger RNA molecules, and therefore multiple proteins, by joining its coding segments in different combinations. In plants, this process is carried out by the spliceosome, a large molecular machine that removes intervening sequences called introns from precursor messenger RNA. Rather than being a rare curiosity, alternative splicing is now understood to be pervasive: studies cited in the review indicate that a large fraction of multi-exon plant genes generate more than one isoform, dramatically expanding the functional repertoire of even a modest genome. Under stress, the splicing pattern of many genes shifts rapidly, allowing a plant to retool its protein output within hours of a stress onset without waiting for new genes to be switched on.

The review highlights several striking examples of this rapid reprogramming. In rice, the heat stress transcription factor OsHSFA2d is alternatively spliced to produce an isoform that participates in the unfolded protein response, a cellular quality-control program activated when high temperatures damage proteins. In Arabidopsis, the serine/arginine-rich splicing factor SR45a not only promotes splicing but also interacts with the nuclear cap-binding complex to modulate the salt-stress response, illustrating that the splicing machinery itself is both a target and an executor of stress signaling. Temperature even acts directly on RNA structure: structural analyses of the tomato heat shock factor HsfA2 pre-messenger RNA show that thermal conditions can alter folding and thereby influence which splice form is produced, a mechanism sometimes described as RNA thermosensing.

Beyond heat, alternative splicing touches nearly every dimension of abiotic stress physiology. A two-staged model of sodium exclusion in rice, built on three-dimensional modeling of HKT transporters, links transporter splicing to salt tolerance. Alternatively spliced transcripts of the rice phytochelatin synthase gene OsPCS2 are implicated in mitigating cadmium and arsenic toxicity, connecting splicing to heavy metal defense. Splicing also maintains mineral nutrient homeostasis in rice, and the splicing pattern of the nitrogen assimilation gene OsGS1;1 affects nitrogen-use efficiency, grain development, and amylose content. In the hormone realm, antagonistic splice variants of HAB1 fine-tune abscisic acid signaling, the master pathway governing drought responses, while splicing variants of the bZIP transcription factor OsABI5 add another layer of ABA-dependent regulation. Even auxin transport is shaped by splicing: mutually opposing PIN7 isoforms are required for tropic growth responses in Arabidopsis.

Long non-coding RNAs represent the second pillar of this regulatory architecture. These transcripts, which exceed roughly 200 nucleotides but generally do not encode proteins, were once dismissed as transcriptional noise—so-called dark matter of the genome. The review traces their rehabilitation into recognized regulators that operate as scaffolds, signal molecules, guides, and competing endogenous RNAs. They act at both transcriptional and post-transcriptional levels, engaging chromatin-modifying machinery, transcription factors, splicing factors, and microRNA pathways. Comparative analyses across 25 flowering plants and pan-transcriptomic surveys have revealed thousands of these transcripts, many of which are dynamically induced or repressed under drought, cold, salt, heat, and nutrient stress.

Concrete functional examples abound in the literature the review synthesizes. In Arabidopsis, a nucleus-localized long non-coding RNA enhances drought and salt tolerance, while the lncRNA APOLO interacts with the transcription factor WRKY42 to trigger root hair cell expansion during cold exposure and can modulate DNA and histone methylation machineries. The antisense transcript of the dormancy quantitative trait locus DOG1 represses seed dormancy to regulate drought tolerance, and transcriptional read-through of the lncRNA SVALKA governs cold acclimation. Cold-induced long antisense transcripts silence a Polycomb target gene, demonstrating how non-coding transcription can reshape epigenetic landscapes. In cotton, the lincRNA XH123 participates in cold-stress regulation, and the polyploidization-activated lncRNA DAN1 was neofunctionalized during drought adaptation, while the lncRNA354 acts as a competing endogenous RNA for miR160b to regulate auxin response factor genes under salt stress in upland cotton.

The competing endogenous RNA mechanism deserves particular attention because it reveals how non-coding RNAs can rewire entire signaling networks. MicroRNAs normally silence target messenger RNAs by guiding cleavage or repressing translation. A lncRNA with binding sites for a given microRNA can sponge that microRNA away, protecting the messenger RNA targets. In rice, the lncRNA TCONS_00021861 is functionally associated with drought tolerance through exactly this ceRNA regulation. In maize, the lncRNA PILNCR2 increases low-phosphate tolerance by interfering with miR399-guided cleavage of phosphate transporter genes of the ZmPHT1 family. This target-mimicry concept, first established in Arabidopsis, provides a mechanistic template for how lncRNAs buffer and redirect microRNA activity under nutrient and water stress.

Perhaps the most forward-looking theme of the review is the emerging evidence that alternative splicing and lncRNAs do not operate in isolation but form an integrated regulatory web. The Arabidopsis lncRNA ASCO modulates the transcriptome through direct interaction with splicing factors, effectively inserting a non-coding RNA into the splicing machinery itself. Epigenetic marks also feed into the system: histone H3 lysine 36 methylation affects temperature-induced alternative splicing and flowering, and DNA methylation changes in Moso bamboo under abiotic stress are associated with altered expression of non-coding RNAs and messenger RNAs. RNA-directed DNA methylation pathways, in which small RNAs guide chromatin modifications, further connect the non-coding transcriptome to epigenetic memory. Together these interactions suggest a coordinated circuit in which splicing, non-coding transcription, and chromatin state continuously inform one another, granting plants the regulatory flexibility to mount graded, reversible, and in some cases memorized responses to recurring stress.

For agriculture, the implications are substantial. Conventional breeding and chemical interventions have delivered gains but remain constrained by cost, time, and genetic limitations, the authors note, bolstering the case for molecular approaches that target RNA regulation directly. Base-editing technologies have already been used to manipulate messenger RNA splicing in plants, opening a path toward precision engineering of stress-responsive isoforms. Multi-omics approaches—integrating transcriptomics, epigenomics, proteomics, and metabolomics—are now identifying the splicing events and lncRNA nodes most relevant to tolerance traits in crops ranging from rice and wheat to cassava, cotton, and citrus. Translating that catalog into durable, field-ready stress resilience will require functional validation of individual isoforms and non-coding transcripts, careful attention to trade-offs between stress tolerance and yield, and methods for delivering RNA-level edits across diverse genetic backgrounds. Still, the review makes a compelling case that the next generation of climate-resilient crops may be written not in new genes, but in the hidden grammar of their RNA.

Subject of Research: RNA-level regulation of plant abiotic stress adaptation through alternative splicing and long non-coding RNAs

Article Title: Regulatory roles of alternative splicing (AS) and long non-coding RNAs (LncRNAs) in plant adaptation to abiotic stresses

Article References: Ghaemi Rad, Z. S., Ahmadikhah, A., & Tohidfar, M. (2026). Regulatory roles of alternative splicing (AS) and long non-coding RNAs (LncRNAs) in plant adaptation to abiotic stresses. 3 Biotech, 16(10), Article 429. https://doi.org/10.1007/s13205-026-05055-9

Image Credits: AI Generated

DOI: 10.1007/s13205-026-05055-9

Keywords: alternative splicing, long non-coding RNAs, abiotic stress, plant stress response, drought tolerance, salt stress, heat stress, spliceosome, competing endogenous RNA, epigenetics, crop improvement, rice

The study, published open access in Cellular and Molecular Life Sciences, describes these cytoplasmic SMN condensates as S-bodies. Under stress conditions such as osmotic challenge, oxidative stress induced by arsenite, or reducing stress induced by dithiothreitol, human lung fibroblasts responded within minutes by assembling these structures along microtubules. Live-cell imaging of cells stably expressing a fluorescently tagged SMN showed that the process is strikingly fast and reversible: when mechanical stress was applied, condensates appeared within seconds, and when osmotic stress was lifted, the assemblies reorganized over the course of recovery. The researchers used indirect immunofluorescence, fluorescence in situ hybridization, and super-resolution STORM microscopy to map the molecular composition and dynamics of these bodies in detail.

What makes S-bodies particularly intriguing is their selectivity. The team showed that they exclude G3BP1, a defining marker of classical stress granules, demonstrating that S-bodies are not simply another flavor of generic stress condensate. Instead, they specifically sequester UsnRNPs that have been mislocalized to the cytoplasm by stress. The assembly of S-bodies also proved independent of ongoing UsnRNP biogenesis: blocking translation with cycloheximide or transcription with NVP2 did not prevent their formation, indicating that the condensation machinery responds to the physical state of the cell rather than to the flux of newly made spliceosomal components.

The recovery phase revealed a second, equally elegant act. As stressed cells returned to normal conditions, the S-bodies did not simply dissolve. Instead, they underwent a microtubule-dependent reorganization into split condensates containing both SMN and CLNS1A, a protein known from the PRMT5 complex that acts earlier in the UsnRNP assembly pathway. The researchers named these dual-compartment structures Janus bodies, after the two-faced Roman god, because they bridge two distinct stages of the assembly line. Within these Janus bodies, SMN colocalized with its interaction partners Gemin2 and DDX20, with methylated Sm proteins, and with the hypermethylated cap structures of UsnRNAs, suggesting that the condensates serve as processing hubs where captured UsnRNPs are evaluated and cleared.

To understand the biophysical basis of this behavior, the authors draw on the concept of liquid-liquid phase separation, or LLPS, the process by which mixtures of proteins and RNAs demix into dense condensates within the cell. Nuclear SMN is already known to condense in Cajal bodies, where it promotes late maturation steps of the spliceosomal machinery. The new work extends this principle to the cytoplasm and assigns it a protective function: rather than participating in assembly, cytoplasmic SMN condensation acts as a buffer, physically sequestering misplaced UsnRNPs so that they cannot interfere with cytoplasmic processes or form aberrant aggregates. The biphasic nature of the response, first sequestration in S-bodies and then resolution through Janus bodies, provides a complete lifecycle for the stress response.

The most clinically resonant finding concerns spinal muscular atrophy, or SMA, a devastating neuromuscular disease caused by loss or deficiency of functional SMN. SMA arises because humans carry a duplicated SMN gene, SMN2, which produces predominantly a truncated protein, SMND7, that lacks exon 7 and is unstable. In cellular models of the disease, including mouse embryonic fibroblasts carrying a humanized SMN2 allele, the researchers found that S-bodies failed to assemble and that cytoplasmic UsnRNPs were not cleared after stress. This failure identifies an impaired tolerance to molecular crowding as a previously unrecognized hallmark of SMA, extending the disease picture beyond the well-established defects in UsnRNP biogenesis and motor neuron survival.

Importantly, the team tested whether pharmacological intervention could restore this protective function. Risdiplam, a small molecule approved for the treatment of SMA that splices SMN2 transcripts productively, was applied to the humanized mouse embryonic fibroblasts. Western blot analysis confirmed that a 24-hour treatment restored SMN expression levels in these cells, raising the possibility that reconstituting sufficient SMN protein also reconstitutes the cytoplasmic condensation response. While the study focuses on cellular models rather than patient neurons, the result suggests that some benefits of SMN-restoring therapies may include the reestablishment of this stress-buffering quality control system, a hypothesis that will require testing in disease-relevant contexts.

The work also reframes how scientists think about the relationship between condensates and the cytoskeleton. The dependence of both S-body maintenance and the transition to Janus bodies on microtubules indicates that phase separation and cytoskeletal transport are not parallel, independent systems but are mechanistically coupled. Microtubules appear to provide the tracks along which the condensates organize, mature, and redistribute during recovery. This coupling may ensure that captured UsnRNPs are routed to specific cellular locations for processing rather than being scattered randomly through the cytoplasm, adding a layer of spatial control to what might otherwise be a simple sequestration mechanism.

Broader implications reach into several active areas of cell biology. The finding that distinct stressors, including osmotic, oxidative, reducing, and mechanical stress, all trigger S-body formation suggests a general response to conditions that perturb molecular crowding. Because UsnRNPs contain uridine-rich small nuclear RNAs, their cytoplasmic accumulation could in principle seed unwanted RNA interactions, and the S-body system may represent an evolved safeguard against such molecular misbehavior. The study also connects to the growing literature on membraneless organelles, stress granules, processing bodies, and U bodies, positioning S-bodies as a distinct member of this family with a dedicated cargo and a defined lifecycle.

For the SMA research community, the identification of condensation defects as a disease phenotype opens new avenues for biomarker development and therapeutic evaluation. If the ability to form S-bodies and clear cytoplasmic UsnRNPs correlates with clinical outcomes, assays based on this cellular response could complement existing measures of SMN protein levels. More fundamentally, the work exemplifies how a protein famous for one role, nuclear assembly of the splicing machinery, can moonlight in an entirely different compartment under stress, and how the failure of that second role may contribute to disease. As the field of biomolecular condensates matures, studies like this one demonstrate that these droplets are not curiosities of physical chemistry but essential, regulated, and clinically relevant machines of cellular housekeeping.

Subject of Research: Stress-induced cytoplasmic SMN condensates that sequester and clear mislocalized UsnRNPs and their failure in spinal muscular atrophy

Article Title: Biphasic SMN condensates safeguard stress-induced cytoplasmic mislocalization of splicing RNPs

Article References: Riedel, Y. L., Dressler, J., Schilling, M. T., & Gruss, O. J. (2026). Biphasic SMN condensates safeguard stress-induced cytoplasmic mislocalization of splicing RNPs. Cellular and Molecular Life Sciences, 83(1), Article 350. https://doi.org/10.1007/s00018-026-06459-9

Image Credits: AI Generated

DOI: 10.1007/s00018-026-06459-9

Keywords: SMN, spinal muscular atrophy, UsnRNP, liquid-liquid phase separation, stress granules, microtubules, Cajal bodies, CLNS1A, spliceosome, Risdiplam, molecular crowding, condensates

Splicing is the process by which the cell’s molecular machinery cuts out non-coding introns from freshly transcribed messenger RNA and stitches the remaining exons together. Far from being a uniform operation, splicing can be regulated so that the same gene yields multiple protein variants depending on which exons are retained or skipped. This alternative splicing is executed by the spliceosome, a massive ribonucleoprotein complex assembled from hundreds of components, including small nuclear ribonucleoproteins and a family of serine-arginine rich proteins known as SR proteins. Cancer cells frequently hijack this machinery, producing splice variants that favor uncontrolled growth, survival under stress, or, as the new study shows, the physical ability to move through tissue.

To find out which splicing factors actually matter for metastatic behavior, the Leiden-led team, spearheaded by first authors Nasi Liu, Jurjun J. S. van der Velde, and Esmee Koedoot under the senior guidance of Sylvia E. Le Dévédec and Bob van de Water, ran a systematic functional screen. Using an imaging-based RNA interference approach, they knocked down each of 244 spliceosome components in two highly motile triple-negative breast cancer cell lines, MDA-MB-231 and Hs578T. Rather than measuring proliferation or viability, the researchers focused on motility itself, deploying phagokinetic track assays, in which cells leave trails as they move across a coated surface, alongside random cell migration assays tracked by high-content microscopy. This design allowed them to quantify migration speed, track geometry, and net displacement for thousands of perturbations in parallel.

The screen’s most striking finding was selectivity. While some spliceosome components, when depleted, broadly impaired cell proliferation or triggered cell death, a distinct subset of splicing factors specifically curtailed cell motility without substantially compromising growth or survival. Among these, SRSF7 stood out as a central regulator. The team confirmed the result with multiple independent methods: siRNA-mediated knockdown, validated at the protein level by western blotting, and inducible CRISPR-Cas9 knockout, in which Cas9 activity and guide RNA expression are switched on with doxycycline. Both approaches converged on the same conclusion: removing SRSF7 sharply reduces the migratory and invasive capacity of triple-negative breast cancer cells in culture.

Crucially, the phenomenon held up in living animals. The researchers used a tail-vein metastasis model, injecting luciferase-labeled cancer cells into mice and tracking lung colonization over time with longitudinal bioluminescent imaging. When SRSF7 was knocked out in the inducible knockout lines, metastatic burden in the lungs dropped dramatically, as confirmed by lung weight measurements and by ink perfusion-based quantification of macrometastases. Notably, the team also examined primary tumor growth in an orthotopic model and found that SRSF7 loss did not simply eliminate the tumor cells; the effect was most pronounced on the cells’ ability to seed and expand metastatic colonies. That distinction matters therapeutically, because a target that specifically disables dissemination could complement existing treatments that shrink primary tumors.

What is SRSF7 actually doing at the molecular level? To answer this, the researchers turned to next-generation RNA sequencing, generating deep transcriptomic datasets from SRSF7-depleted cells in both cell lines and from two independent CRISPR knockout clones. Differential gene-expression analysis revealed that SRSF7 loss broadly downregulates a coordinated program of genes involved in extracellular matrix organization, cell-matrix adhesion, integrin signaling, and cytoskeletal regulation. In other words, SRSF7 does not merely tweak a single migration gene; it maintains the molecular infrastructure that allows a cancer cell to grip the matrix, remodel its surroundings, and propel itself forward. Pathway enrichment analyses using Reactome and KEGG databases confirmed the coherence of this program across cell lines and across knockdown and knockout modalities.

The sequencing data went further, cataloguing thousands of SRSF7-dependent alternative splicing events. Among these, recurrent exon-skipping alterations stood out, affecting genes with established roles in migratory and adhesive phenotypes. The researchers quantified these events using the percentage-spliced-in metric, comparing inclusion levels between control and SRSF7-depleted conditions, and found strong concordance between the two independent knockout clones. They also observed that SRSF7 knockout reduced the inclusion of a poison cassette exon within the SRSF7 locus itself, a self-regulatory feedback element in which the retained exon introduces a premature stop codon that degrades the transcript. This autoregulatory loop suggests that cells may have an intrinsic mechanism for damping SRSF7 levels, one that metastatic cancer cells appear to override.

The clinical relevance of these findings was tested against patient data. By mining triple-negative breast cancer gene-expression cohorts, including data from The Cancer Genome Atlas, the team showed that elevated SRSF7 expression correlates with poorer survival outcomes, including measures of overall, disease-free, and metastasis-free survival. Candidate splicing factors identified in the screen, including SRSF7, were also expressed at higher levels in tumor tissue than in normal breast tissue, in triple-negative tumors compared with estrogen receptor-positive tumors, and in basal-like breast cancer cell lines compared with luminal lines. Expression of the candidates additionally increased with pathologic stage, tying the molecular biology of the screen directly to the trajectory of human disease.

The study also carries implications for how splicing-directed therapies might be developed. Broad spliceosome inhibitors, such as compounds that trap the U2 small nuclear ribonucleoprotein complex onto pre-messenger RNA, have shown activity in myelodysplastic syndromes and some solid tumors, but their toxicity profile reflects the fact that every cell needs splicing. The Leiden and Erasmus findings suggest a more refined strategy: because certain splicing factors like SRSF7 are selectively required for metastatic behavior rather than basic viability, tumors may harbor splicing-factor dependencies that can be exploited at doses or with modalities that spare normal tissue. The observation that SRSF7 depletion suppresses lung colonization while leaving proliferation largely intact in vitro hints at a therapeutic window, although translating that into a clinical intervention will require selective ways to inhibit or degrade SRSF7, a challenge the field of RNA-binding protein drug discovery is actively pursuing.

For now, the work delivers something triple-negative breast cancer research has long needed: a systematic, unbiased map of which parts of the splicing machinery actually drive metastasis, validated from cultured cells through animal models to patient cohorts. It reframes metastasis as a disease of information processing, in which the way RNA transcripts are assembled determines whether a tumor cell stays put or spreads. With the European Research Council and the Dutch Cancer Society supporting the program, and with the underlying datasets and models now published, the researchers and the wider field can begin testing whether targeting SRSF7 and its splicing network can turn one of cancer’s most lethal capabilities into its Achilles’ heel.

Subject of Research: The role of the RNA splicing factor SRSF7 in regulating metastatic programs in triple-negative breast cancer

Article Title: SRSF7 controls RNA splicing programs driving triple-negative breast cancer metastasis

Article References: Liu, N., van der Velde, J. J. S., Koedoot, E., Smid, M., de Weerd, V., Martens, J. W. M., Le Dévédec, S. E., & van de Water, B. (2026). SRSF7 controls RNA splicing programs driving triple-negative breast cancer metastasis. Journal of Experimental & Clinical Cancer Research. https://doi.org/10.1186/s13046-026-03817-0

Image Credits: AI Generated

DOI: 10.1186/s13046-026-03817-0

Keywords: triple-negative breast cancer, SRSF7, RNA splicing, splicing factor, metastasis, spliceosome, alternative splicing, cell migration, CRISPR-Cas9, extracellular matrix, integrin signaling, cancer genomics

Splicing is the molecular editing step that removes non-coding introns from freshly made RNA transcripts and joins the protein-coding exons together. The machinery responsible, the spliceosome, must identify precise boundaries between exons and introns, most critically the 3′ splice site that marks the end of an intron. In most human genes, this task is made easier by the underlying nucleotide composition: exons tend to be rich in guanine and cytosine, the G and C of the DNA alphabet, while the surrounding introns are rich in adenine and thymine. That contrast gives the splicing machinery a clear signal of where exons begin and end. But a distinct subset of genes breaks this rule. In these genes, both exons and introns are GC-rich, producing a GC-leveled architecture in which the usual compositional contrast between coding and non-coding regions largely disappears.

That architectural quirk has consequences. When exons and introns carry similar GC content, the spliceosome loses one of its strongest clues for distinguishing exon from intron, and the 3′ splice sites in these genes tend to be cytosine-rich and depleted of thymine, features that make them intrinsically weak substrates for recognition by the splicing machinery. The new study set out to determine how cells manage to splice these difficult genes efficiently despite their unfavorable sequence landscape. The answer, the researchers report, lies in a compartment that has fascinated cell biologists for decades: the nuclear speckle.

Nuclear speckles are membraneless organelles, dense droplet-like structures within the nucleus that are packed with RNA-processing factors, including many components of the spliceosome. Rather than being passive storage depots, speckles are now understood to function as dynamic hubs for RNA metabolism, exchanging factors with nearby genes and concentrating the molecular tools needed for transcript maturation. Recent work has shown that speckles are largely organized by two large scaffold proteins, SON and SRRM2, and that genes located in close spatial proximity to speckles tend to be spliced more efficiently than genes farther away. What remained unclear was the molecular mechanism connecting that spatial coupling to the actual chemistry of splicing.

The Zhejiang University team, led by corresponding author Yafei Yin with important contributions from Xiaoyu Li, approached the question by combining acute protein depletion with a battery of genome-wide assays. Using the dTAG degron system, a technique that allows rapid and targeted destruction of a chosen protein inside living cells, the researchers generated cell lines in which SON could be eliminated on demand. They then profiled the consequences using 4sU-seq, which captures newly synthesized RNA and therefore reports directly on splicing efficiency in real time, along with CLIP-seq and TurboRIP-seq to map where SON binds and which RNA-protein complexes it associates with, U2 RAP-seq to follow the recruitment of the U2 spliceosomal component to pre-messenger RNA, and Pol II ChIP-seq to track the behavior of the RNA polymerase II enzyme that transcribes genes into RNA. All of the resulting datasets have been deposited in the NCBI Gene Expression Omnibus under accession number GSE325871, allowing other researchers to examine the raw evidence.

The data converged on a clear conclusion. When SON was removed, splicing defects appeared preferentially in GC-rich genes, precisely the subset whose weak, cytosine-rich and thymine-poor 3′ splice sites make them dependent on extra help. The mechanism the authors propose is that SON stabilizes the recognition of those weak splice sites, effectively propping up the first and most error-prone step of spliceosome assembly at GC-rich intron boundaries. In other words, SON does not change the sequence of the gene, but it changes the probability that the splicing machinery correctly interprets a difficult sequence, converting what would otherwise be inefficient and error-prone processing into fast, accurate exon joining.

This mechanism elegantly explains why GC-leveled genes cluster near nuclear speckles in the first place. If a gene’s splice sites are inherently weak, the gene benefits from sitting close to a reservoir of concentrated splicing factors, and SON, as a core scaffold of the speckle, appears to be the factor that translates physical proximity into biochemical support. The finding also assigns a concrete molecular role to SON that goes beyond its established architectural function in organizing speckle structure alongside SRRM2. SON, the study suggests, is not merely a beam holding the nuclear compartment together; it is an active participant in the splicing reactions that the compartment enables.

The implications reach beyond basic cell biology. SON has previously been implicated in human disease, and genes with GC-rich, GC-leveled architecture include many regulators of development and cell growth, so understanding how their splicing is safeguarded could illuminate why nuclear organization fails in certain disorders. The work also connects to a broader theme in modern biology: the recognition that genome function depends on spatial organization, with the position of a gene relative to nuclear bodies influencing how efficiently it is expressed. By identifying the sequence feature, the weak 3′ splice site, that makes a gene dependent on speckle proximity, the study provides a concrete molecular bridge between nuclear geography and RNA chemistry, a bridge that has been hypothesized but never resolved in such detail.

Technically, the study stands out for its use of complementary high-throughput methods applied after acute, rather than chronic, protein loss. Chronic depletion experiments can be confounded by secondary effects as cells adapt over days, whereas the dTAG system destroys SON within hours, allowing the researchers to observe the primary consequences of its absence. The combination of nascent RNA sequencing with crosslinking-based binding maps and polymerase occupancy data allowed the team to distinguish direct effects on splice-site recognition from indirect effects on transcription or RNA stability, strengthening the causal chain from SON binding to efficient splicing of GC-rich transcripts.

Open questions remain. The precise molecular contacts through which SON stabilizes 3′ splice-site recognition, whether through direct binding to the weak cytosine-rich sites, through recruitment of U2 snRNP components, or through both routes acting in concert, will require structural and biochemical follow-up. It also remains to be seen whether other speckle components, including the co-scaffold SRRM2, contribute redundant or specialized support for different classes of weak splice sites. Nevertheless, by demonstrating that a single nuclear speckle protein safeguards the splicing of an entire architectural class of genes, the study transforms nuclear speckles from a correlated curiosity into a mechanistically understood support system, and it gives researchers a new lens for examining how the architecture of the genome and the architecture of the nucleus co-evolved to make complex gene expression possible.

Subject of Research: Role of the nuclear speckle protein SON in the splicing of GC-rich genes

Article Title: Nuclear speckle protein SON safeguards efficient splicing of GC-rich genes

Article References: Fan, W., Zhou, Y., Zhang, X., Tong, C., Li, X., & Yin, Y. (2026). Nuclear speckle protein SON safeguards efficient splicing of GC-rich genes. Cell Research. https://doi.org/10.1038/s41422-026-01303-y

Image Credits: AI Generated

DOI: 10.1038/s41422-026-01303-y

Keywords: nuclear speckles, SON, RNA splicing, GC-rich genes, spliceosome, 3′ splice site, dTAG degron, 4sU-seq, CLIP-seq, nuclear organization, pre-mRNA processing, Cell Research

Retinitis pigmentosa, also known as rod-cone dystrophy, is one of the most genetically heterogeneous disorders in human medicine. It begins with the progressive loss of rod photoreceptors, the cells responsible for vision in dim light, which produces night blindness and narrowing of the visual field. As the disease advances, cone photoreceptors, which mediate daylight and color vision, degenerate as well, often culminating in severe visual impairment or legal blindness in midlife. Approximately forty genes have so far been linked to the autosomal dominant form of the disease, in which a single inherited copy of a pathogenic variant is sufficient to cause symptoms. Yet even with modern genetic testing, a stubborn fraction of patients never receives a molecular diagnosis.

That diagnostic gap was precisely what motivated the new study. The researchers, led by Isabelle Audo and Christina Zeitz of Sorbonne Université, INSERM, CNRS and the Institut de la Vision in Paris, together with colleagues at the Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts and partner institutions, analyzed a French cohort of 395 families with autosomal dominant retinitis pigmentosa and 418 genetically unsolved cases. Every participant underwent comprehensive ophthalmic examination, including standard-of-care retinal imaging and functional assessments, ensuring that the genetic findings could be interpreted against detailed clinical pictures. The team combined genome sequencing, direct Sanger sequencing and a candidate gene approach to interrogate regions of the genome that standard analyses often skip.

The regions they targeted belong to a family of genes with an unusual biology. Small nuclear RNA genes do not encode proteins; instead, they produce short RNA molecules that form the structural and catalytic core of the spliceosome, the cellular machine that removes intervening sequences from messenger RNA precursors. The U4 and U6 small nuclear RNAs associate with U5 snRNA and a set of proteins to build the tri-small nuclear ribonucleoprotein complex, or tri-snRNP, a central component of the major spliceosome. Because splicing is essential in every cell, one might expect defects in these genes to be lethal or to cause widespread damage. Instead, recent years have revealed a striking pattern: inherited and de novo variants in snRNA genes appear in people with recessive neurodevelopmental disorders, and, as the new work confirms, in people with inherited retinal degeneration.

What makes the retinal findings particularly intriguing is where the disease-causing variants sit within these small RNA genes. The variants associated with retinitis pigmentosa cluster in regions that are distinct from those implicated in neurodevelopmental disorders, and they affect domains involved in the assembly of the tri-snRNP with three proteins that retinitis specialists know well: PRPF3, PRPF8 and PRPF31. All three of these proteins are themselves established causes of autosomal dominant retinitis pigmentosa. In other words, the retina appears to be exquisitely sensitive to a specific kind of disruption in the splicing machinery, one that interferes with the assembly of the tri-snRNP complex, while other tissues tolerate it. This convergence of RNA genes and spliceosome protein genes on the same disease phenotype provides a coherent mechanistic thread through what had seemed like scattered genetic findings.

The results of the cohort screen were unambiguous. The researchers identified heterozygous inherited variants in RNU4-2 and in RNU6 paralogs in eight unrelated families with non-syndromic autosomal dominant retinitis pigmentosa. In every family where additional members were available for testing, the variant co-segregated with the disease, passing from affected parents to affected children exactly as an autosomal dominant mutation should. None of the affected individuals showed the extra-neurological features that might suggest a syndromal diagnosis; their disease was confined to the retina, reinforcing the idea that these snRNA variants produce a pure retinal phenotype rather than a broader developmental syndrome.

Translated into population terms, the eight families mean that variants in RNU4-2 or RNU6 paralogs account for two percent of the genetically solved individuals with autosomal dominant retinitis pigmentosa in the cohort. Perhaps more striking is the comparison the authors draw within the spliceosome category: these snRNA variants represent six percent of all individuals carrying variants in genes coding for the multi-subunit spliceosome complex. A single family of non-coding RNA genes therefore contributes a non-trivial share of the spliceosome-related disease burden, a category that until now has been defined almost entirely by protein-coding genes such as PRPF31, PRPF8, PRPF3, PRPF4, PRPF6, SNRNP200 and RP9. The message for diagnostics is clear: excluding snRNA genes from analysis leaves a measurable fraction of patients without answers.

Why have these genes escaped detection for so long? The answer lies partly in the mechanics of genome analysis. Small nuclear RNA genes are short, repetitive and often present in multiple copies or paralogs scattered across the genome, which complicates the alignment of sequencing reads and the confident calling of variants. Many bioinformatics pipelines are tuned to detect single nucleotide changes in protein-coding exons and simply do not report variants in these loci, even when the underlying sequence data contain them. The French team’s use of genome sequencing combined with targeted Sanger validation illustrates the practical path forward: once a candidate snRNA variant is flagged, conventional sequencing can confirm it and family studies can establish segregation. The bottleneck is not the technology but the willingness to look in places the standard tools ignore.

The clinical implications extend beyond diagnosis. A confirmed molecular diagnosis is the gateway to genetic counseling, allowing affected individuals to understand the inheritance pattern and recurrence risk in their families, and to reproductive options such as preimplantation genetic testing. It is also increasingly the entry ticket to precision therapy, as gene-specific clinical trials for inherited retinal disease multiply. For the two percent of autosomal dominant retinitis pigmentosa patients who carry RNU4-2 or RNU6 paralog variants, inclusion of snRNA genes in diagnostic panels could mean the difference between an unsolved case and eligibility for emerging interventions. The finding also suggests that other unexplained retinal degenerations might owe their existence to additional non-coding RNA genes waiting to be interrogated.

Scientifically, the study strengthens an emerging view of the spliceosome as a hotspot for tissue-specific disease. The retina, with its extraordinarily high metabolic demands and its photoreceptors’ constant need to renew outer segment proteins, appears uniquely vulnerable to partial defects in RNA processing that other tissues can buffer. The clustering of retinal disease variants in tri-snRNP assembly domains, distinct from the regions implicated in neurodevelopmental disorders, hints at a genotype-phenotype map within molecules barely a hundred nucleotides long. As genome sequencing becomes the default first test for rare disease, the French cohort results argue that the small RNAs at the heart of the spliceosome deserve a permanent place on the diagnostic checklist, both for the patients they will finally explain and for the biology they continue to reveal.

Subject of Research: Small nuclear RNA gene variants causing autosomal dominant retinitis pigmentosa

Article Title: Variants in RNU4-2 or RNU6 paralogs account for 2% of individuals with non-syndromic autosomal dominant retinitis pigmentosa in a large French cohort

Article References: Audo, I., Navarro, J., Bianco, L., Antropoli, A., Condroyer, C., Antonio, A., Andrieu, C., Mohand-Saïd, S., Laurent-Coriat, C., Atia, R., Benadji, A., Smirnov, V., Sahel, J.-A., & Zeitz, C. (2026). Variants in RNU4-2 or RNU6 paralogs account for 2% of individuals with non-syndromic autosomal dominant retinitis pigmentosa in a large French cohort. Genome Medicine. https://doi.org/10.1186/s13073-026-01743-6

Image Credits: AI Generated

DOI: 10.1186/s13073-026-01743-6

Keywords: retinitis pigmentosa, RNU4-2, RNU6, small nuclear RNA, spliceosome, tri-snRNP, inherited retinal disease, genome sequencing, autosomal dominant inheritance, RNA splicing, genetic diagnosis, French cohort