The work is especially relevant to Williams-Beuren syndrome, a rare genetic disorder caused by the deletion of a segment of chromosome 7. Most people with the syndrome also lose one copy of NSUN5, a gene encoding an enzyme that modifies ribosomal RNA. Williams-Beuren syndrome is associated with a distinctive pattern of physical and cognitive traits, as well as frequent sleep disturbances. Yet the biological pathway linking the missing gene to abnormal sleep has remained unclear. The new research, conducted by scientists at Fudan University and collaborating institutions, indicates that NSUN5 deficiency could contribute to sleep problems through damage to white matter rather than through a simple failure of the brain’s sleep clock.

NSUN5 belongs to a family of RNA-modifying enzymes that add chemical marks to RNA molecules. In this case, the enzyme installs 5-methylcytosine, or m5C, at a specific site on 28S ribosomal RNA. Ribosomes are the cell’s protein-making complexes, assembled from ribosomal RNA and proteins. They read messenger RNA and translate its nucleotide sequence into chains of amino acids. Although ribosomal RNA is sometimes regarded as a passive scaffold, chemical modifications can alter how ribosomes interact with messenger RNAs and how efficiently they translate particular groups of genes. The researchers therefore asked whether loss of Nsun5 would shut down protein synthesis broadly or instead cause a more selective imbalance in which proteins cells produce.

To investigate the question, the team created Nsun5-knockout mice and compared them with genetically normal animals. The researchers combined electroencephalography, which records electrical activity in the brain, with electromyography, which measures muscle activity, to identify sleep states and their timing. They also used RNA sequencing to measure gene transcription, ribosome profiling to determine which messenger RNAs were actively being translated, and nascent proteomics to track newly produced proteins. Conventional proteomics provided a second view of protein abundance, while transmission electron microscopy examined the fine structure of myelin. Positron emission tomography combined with computed tomography was used to map regional brain metabolism.

The first molecular result was clear: eliminating Nsun5 sharply reduced m5C modification on 28S ribosomal RNA. But the consequence was not a global collapse of translation. Instead, the knockout animals showed selective translational dysregulation. This distinction is important. A wholesale failure of ribosomes would be expected to impair nearly every cellular process and likely produce severe developmental abnormalities. Selective dysregulation implies that some messenger RNAs, or groups of related transcripts, are more sensitive than others to changes in ribosomal composition or activity. In the Nsun5-deficient mice, the affected programs were enriched for genes involved in myelination and for subunits of voltage-gated potassium channels.

Myelin is produced primarily by oligodendrocytes in the central nervous system. These specialized glial cells extend processes around axons, forming multilayered sheaths that electrically insulate nerve fibers. The insulation allows electrical impulses to travel rapidly by jumping between exposed gaps known as nodes of Ranvier, a process called saltatory conduction. If myelin becomes thin, patchy or structurally disorganized, signals can slow, fail or arrive out of sequence. The corpus callosum, the large bundle of fibers connecting the brain’s two hemispheres, was particularly affected in the knockout mice. The animals had fewer oligodendrocytes and diffuse hypomyelination, meaning that axons retained less of the normal insulating sheath.

The study also identified changes in Kcna1 and Kcna2, genes that encode voltage-gated potassium channel subunits. These channels help neurons restore their electrical state after firing and regulate the timing, duration and frequency of action potentials. Their altered translation provides a possible second route from Nsun5 loss to abnormal neural activity. A neuron communicating across a poorly insulated axon already faces problems with signal propagation; altered potassium-channel abundance could further change excitability and firing precision. Together, defects in myelin and ion-channel regulation could disturb the distributed networks that coordinate transitions between wakefulness, non-rapid-eye-movement sleep and rapid-eye-movement sleep.

The physiological effects were evident in the animals’ sleep recordings. Nsun5-knockout mice spent less time in non-rapid-eye-movement sleep and displayed altered organization of sleep during the night, when mice are normally active but also cycle through distinct sleep states. Sleep disruption was accompanied by increased regional cortical metabolic activity detected with fluorodeoxyglucose PET. Higher glucose uptake does not necessarily mean that brain function is improved; in this context, it may reflect excessive or poorly coordinated activity in cortical regions whose white-matter connections have been compromised. The result is consistent with a nervous system working harder or firing abnormally while failing to generate stable sleep.

The researchers then tested whether the phenotype could be reversed pharmacologically. Clemastine, an antihistamine that has attracted interest as a potential remyelinating drug, significantly improved sleep abnormalities in the Nsun5-knockout mice and restored the integrity of myelin. The study also tested 4-aminopyridine, a potassium-channel blocker that can improve conduction in demyelinated axons by prolonging action potentials and increasing the probability of neurotransmitter release. Treatment with 4-aminopyridine alleviated the sleep phenotype as well. Because the two compounds act through different mechanisms—one promoting myelin repair and the other modifying electrical conduction—the results support the idea that both white-matter damage and altered potassium-channel function contribute to the disorder.

The findings do not yet establish that NSUN5 loss causes sleep disruption in people with Williams-Beuren syndrome, nor do they show that either drug is a treatment for that condition. The experiments were performed in genetically engineered mice, and mouse sleep architecture, brain development and drug responses are not identical to those of humans. The study also does not determine whether myelin damage is the initiating event or whether altered neural activity and glial biology reinforce one another in a feedback loop. Nevertheless, it provides a mechanistic framework that connects an RNA modification to protein-selective translation, oligodendrocyte and myelin loss, ion-channel imbalance and abnormal sleep. The researchers’ results raise the possibility that sleep disturbance in Williams-Beuren syndrome and other white-matter disorders could be more than a symptom: it may be a measurable consequence of disrupted molecular control over the brain’s wiring and electrical communication.

Subject of Research: The role of Nsun5-dependent ribosomal RNA methylation in myelin integrity, white-matter function and sleep regulation

Article Title: Nsun5 deficiency leads to impaired myelin integrity and sleep disruption

Article References: Chen, P., Zhao, H., Liu, C. et al. “Nsun5 deficiency leads to impaired myelin integrity and sleep disruption.” BMC Medicine (2026). Original research article

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05160-9

Keywords: Nsun5, ribosomal RNA methylation, myelin sheath, white matter, sleep disruption, Williams-Beuren syndrome, oligodendrocytes, potassium channels, ribosome profiling

Although Babesia divergens is not a virus, its biology is highly relevant to infectious-disease science because it depends on a host organism, is transmitted by ticks and can produce rapidly advancing illness in susceptible people. The parasite belongs to the apicomplexans, a diverse group that also includes the organisms responsible for malaria and toxoplasmosis. Understanding how its cells build proteins may reveal vulnerabilities that are invisible when researchers focus only on the parasite’s genome or on the molecules involved in transmission.

Ribosomes are often described as the “protein factories” of cells, but that phrase conceals their complexity. Each ribosome is a molecular machine made from ribosomal proteins and several RNA molecules. It reads messenger RNA, matches genetic instructions with transfer RNAs and links amino acids into proteins. In eukaryotic parasites, ribosomes are assembled through highly coordinated steps in which precursor rRNAs are processed, chemically modified and combined with proteins. Small changes in this process can influence how efficiently a ribosome translates particular messenger RNAs, how it responds to stress and how it adapts to different environments.

The new work focuses on the architecture of the B. divergens ribosome and maps its rRNA modification landscape. rRNA modifications are chemical alterations added after, or during, the synthesis of ribosomal RNA. Common examples include methylation, in which a methyl group is attached to a nucleotide, and pseudouridylation, in which uridine is converted into the related nucleotide pseudouridine. These changes can stabilize RNA structure, influence the geometry of the ribosome’s functional centers and help ensure accurate decoding of messenger RNA.

For a parasite that moves between ticks and vertebrate hosts, such molecular flexibility may be especially important. The environments encountered during the parasite’s life cycle differ sharply in temperature, nutrient availability, immune pressure and cellular context. Inside red blood cells, B. divergens must acquire nutrients and replicate while avoiding elimination by the host. In the tick, it faces a different set of biological conditions. A ribosome is not simply a static structure in this setting; its composition and chemical state may help determine how efficiently the parasite can produce proteins under changing pressures.

Mapping the modification landscape also adds a layer of information that cannot be obtained from DNA sequence alone. The genes encoding rRNAs indicate the basic blueprint, but they do not fully reveal which nucleotides are chemically modified, when those modifications are installed or how they affect ribosome performance. By combining structural analysis with molecular characterization, studies of this kind can distinguish conserved features shared across eukaryotes from lineage-specific adaptations that emerged during parasite evolution.

That distinction matters for drug discovery. Many antimicrobial compounds work by targeting ribosomes, but differences between pathogen and host ribosomes are essential for achieving selective toxicity. A compound that blocks protein synthesis in a parasite while sparing human cells could provide a powerful therapeutic strategy. The challenge is that ribosomes are ancient and highly conserved, meaning that a drug aimed at a shared functional site may also damage host cells. Parasite-specific architecture or unusual rRNA modifications could point toward more precise targets.

The study may also help explain why existing drugs do not always perform consistently against tick-borne parasites. Resistance can arise through changes in drug-binding sites, altered transport or increased capacity to repair cellular damage. Ribosomal differences could represent another layer of variation, affecting how a compound interacts with the translation machinery or how the parasite maintains protein production during treatment. Detailed structural information can therefore support the design of inhibitors that exploit features unique to B. divergens rather than relying on broad-spectrum mechanisms.

Beyond therapy, the findings contribute to a broader effort to understand how apicomplexan parasites evolved. Their ribosomes are related to those of other eukaryotes, yet parasite lineages have accumulated distinctive molecular traits as they adapted to complex life cycles. Comparing B. divergens with malaria parasites and other apicomplexans could reveal which ribosomal features are ancient and which arose independently. Such comparisons may clarify how changes in RNA processing and ribosome assembly support parasitism, host switching and transmission by arthropods.

The research does not turn the ribosome into a simple answer to the medical challenges posed by babesiosis, and structural discoveries must eventually be tested through functional experiments, drug screens and studies in infection models. Even so, defining the ribosomal architecture and rRNA modification landscape of B. divergens provides a more complete molecular portrait of a pathogen that has received less attention than malaria despite its capacity to cause life-threatening disease. By showing how this parasite’s protein-making machinery is organized and chemically tuned, the study establishes a foundation for future work on parasite-specific therapeutics, diagnostic markers and the evolutionary biology of tick-borne infection.

Subject of Research: Ribosomal architecture and ribosomal RNA modification landscape in the tick-borne parasite Babesia divergens

Article Title: Ribosomal architecture and rRNA modification landscape in the tick-borne parasite Babesia divergens

Article References: Gutierrez-Vargas, C., Izhaki-Tavor, L.S., Calvopina-Chavez, D.G. et al. “Ribosomal architecture and rRNA modification landscape in the tick-borne parasite Babesia divergens.” Nature Communications (2026). https://doi.org/10.1038/s41467-026-75282-4

Image Credits: AI Generated

DOI: 10.1038/s41467-026-75282-4

Keywords: Babesia divergens, babesiosis, tick-borne parasite, ribosome, ribosomal RNA, rRNA modifications, parasite biology, protein synthesis, structural biology, infectious disease