Bacteria Use a Telomerase-Like Reverse Transcriptase to Fight Off Viruses

Bacteria are locked in a perpetual arms race with the viruses that infect them, known as phages, and the defensive weapons they have evolved are proving far stranger than scientists imagined. In a study published in Nature, a team led by Samuel H. Sternberg of Columbia University, together with collaborators at the University of Copenhagen, the Simons Electron Microscopy Center, and institutions in Spain, describes a previously unknown bacterial antiviral system called DRT10 that builds long, repetitive strands of DNA from an RNA template. The machinery at the heart of this system is a reverse transcriptase, an enzyme that copies RNA into DNA, and its mode of operation bears a striking resemblance to telomerase, the celebrated enzyme that maintains the protective caps at the ends of eukaryotic chromosomes. The discovery not only adds a new entry to the growing catalogue of bacterial immune strategies but also hints at a deep evolutionary kinship between bacterial defense enzymes and the telomerase that safeguards our own genomes.

Defense-associated reverse transcriptases, abbreviated DRTs, form a diverse family of enzymes that bacteria deploy to repel phage infection. Unlike the reverse transcriptases encoded by retroviruses such as HIV, which convert viral RNA genomes into DNA for integration into the host, DRTs appear to have been repurposed entirely for defense. In recent years, researchers have characterized several members of this family, including DRT2, DRT3, and DRT9, each of which uses cDNA synthesis in a distinctive way to detect or neutralize invading viruses. Yet the majority of DRT systems remain unexplored, their mechanisms hidden within the vast sequence space of bacterial genomes. The new study set out to illuminate one such dark corner of the family and, in doing so, uncovered a mechanism with unexpected parallels to one of molecular biology’s most famous enzymes.

The DRT10 system consists of two components: a reverse transcriptase protein and an associated noncoding RNA, an RNA molecule that does not encode a protein but instead serves a structural or functional role. When the researchers reconstituted the system in the laboratory, they found that the enzyme catalyzes a processive, protein-primed synthesis of tandem-repeat DNA. In other words, once initiated on a protein primer, the reverse transcriptase repeatedly copies the same segment of the noncoding RNA template over and over, churning out a long DNA product composed of head-to-tail repeats. This iterative mode of polymerization is the defining feature that links DRT10 to telomerase, which likewise adds repetitive DNA sequences, the telomeric repeats, again and again to chromosome ends using its own built-in RNA template.

A central question in understanding such systems is which part of the RNA serves as the template for repeat addition. The team found that reverse transcription in the DRT10 system is templated by a defined region of the noncoding RNA characterized by a distinctive sequence pattern, and that the template is flanked by template boundary elements. Both the sequence pattern and the boundary elements are conserved across related systems, and both proved essential for DNA repeat addition in biochemical assays. This architecture solves a fundamental problem for any enzyme that copies the same template repeatedly: how does the polymerase know where the template begins and ends so that it resets after each round rather than drifting off the RNA? The boundary elements act as molecular fences, delimiting the stretch of RNA that is copied and enabling the enzyme to cycle back and synthesize the next repeat in the tandem array.

To see how the protein and RNA components are physically organized, the researchers turned to cryo-electron microscopy, a technique that flash-freezes molecular complexes and images thousands of copies to reconstruct their three-dimensional structure. The reconstructions revealed an unanticipated 2:1 architecture: two reverse transcriptase monomers bind to opposite sides of a single pseudo-symmetric noncoding RNA molecule. The RNA, in effect, acts as a scaffold that dimerizes the enzyme, presenting two template regions, one to each monomer. This two-fold symmetric arrangement was not predicted from sequence analysis alone and illustrates how noncoding RNAs can choreograph the assembly of multi-enzyme complexes in ways that protein-only systems do not.

Biochemical experiments then dissected what each of the two bound monomers actually does. The results showed that each reverse transcriptase monomer reverse transcribes the template encoded on its respective side of the noncoding RNA, but only one of the two generates the long repetitive product. The identity of that productive template is defined by the distance between two flanking stem-loop anchors, structured elements in the RNA that bracket the template region. By varying this distance, the researchers could alter the properties of the synthesized DNA, demonstrating that the RNA scaffold does more than merely position the enzymes: it actively specifies which template is used for processive repeat synthesis. The second monomer, meanwhile, copies its own template without producing the long repetitive cDNA, a division of labor whose functional consequences for antiviral defense remain an open question.

The mechanistic echoes of telomerase are hard to miss. Telomerase carries its own RNA subunit with a short template segment, uses boundary elements to keep the enzyme copying only that segment, and repeatedly adds telomeric repeats to chromosome termini through iterative cycles of template positioning and DNA synthesis. The mode of iterative, boundary-delimited cDNA synthesis observed for DRT10 exhibits direct parallels to this process, despite the two systems operating in organisms separated by billions of years of evolution and serving entirely different biological purposes, one defending bacteria against phages and the other preserving chromosome integrity in eukaryotes. The convergence on the same polymerization logic suggests that iterative templated repeat addition is a particularly effective solution to a recurring biochemical problem.

That suggestion gains weight from the study’s phylogenetic analyses. When the researchers built evolutionary trees of reverse transcriptases across the domains of life, telomerase did not appear as an isolated lineage. Instead, it fell within a monophyletic clade together with the DRT family, meaning that telomerase and these bacterial defense enzymes appear to share a common ancestor. The implication is provocative: the DNA polymerization activity of telomerase, long studied as a eukaryotic specialization, may have roots in the ancient bacterial machinery of antiviral defense. If so, the telomere-maintaining enzymes that influence aging and cancer in humans would represent evolutionary descendants of, or at least relatives of, molecular weapons that bacteria once wielded against their viruses.

Together with earlier work on DRT2, DRT3, and DRT9, the new findings point to a conserved mechanistic logic underlying RNA-templated DNA repeat addition across diverse DRT systems, even as those systems arrive at vastly different architectural solutions. Some use single enzymes, others dimeric assemblies; some employ protein priming, others rely on different initiation strategies; yet all converge on the core idea of using a noncoding RNA template, delimited by structural boundaries, to generate repetitive cDNA. This recurring design principle now stands as a unifying theme in a rapidly expanding branch of bacterial immunity research, one in which reverse transcription, once considered a viral specialty, has become a central player.

The work also broadens the known repertoire of reverse-transcription-based antiviral strategies in bacteria, a catalogue that biotechnologists are watching closely. Bacterial defense systems have repeatedly proven fertile ground for molecular tools, with CRISPR being the most famous example, and enzymes that synthesize DNA from RNA templates with programmable specificity hold obvious appeal for genome engineering, molecular recording, and biosensing applications. While the immediate significance of the study lies in basic biology, revealing how a bacterial immune system works at atomic and mechanistic resolution, the deep evolutionary link it draws between phage defense and telomerase ensures that its implications will reach well beyond microbiology, touching questions about the origins of the very machinery that protects the chromosomes of complex life.

Subject of Research: A bacterial antiviral defense system that uses telomerase-like reverse transcription to synthesize tandem-repeat DNA

Article Title: Antiviral immunity via telomerase-like reverse transcription in bacteria

Article References: Tang, S., Ramirez, J. L., He, Q., Rodríguez Mestre, M., Wiegand, T., Zhang, D. J., Wang, M., Lampe, G. D., Wang, J., Ma, Y., Jovanovic, M., Pinilla-Redondo, R., Fernández, I. S., & Sternberg, S. H. (2026). Antiviral immunity via telomerase-like reverse transcription in bacteria. Nature. https://doi.org/10.1038/s41586-026-11250-8

Image Credits: AI Generated

DOI: 10.1038/s41586-026-11250-8

Keywords: antiviral immunity, reverse transcriptase, telomerase, bacterial defense, noncoding RNA, cryo-electron microscopy, phage biology, cDNA synthesis, molecular evolution, DRT10, tandem-repeat DNA, CRISPR