Bacterial Antiviral Enzyme and Human Telomerase May Share a Common Ancestor

A bacterium trying to fend off an invading phage has limited options: cut it, copy viral RNA for recognition—or rewrite its own DNA so the invader can't recognize it.

A paper published in *Nature* on October 12 by the Sternberg Lab at Columbia University describes the strangest version of that third strategy: bacteria using a reverse transcriptase, with a self-encoded RNA as template, to synthesize a long string of head-to-tail repeated DNA.

The system is called DRT10.

🧬 Two Enzymes on One RNA, Only One Working

DRT10 binds a non-coding RNA and catalyzes continuous, protein-primed tandem repeat DNA synthesis. The reverse-transcription template is a defined region of that RNA, carrying a characteristic sequence pattern and template boundary elements—both conserved, both required for repeat addition.

Cryo-EM reconstruction revealed an unexpected structure: two reverse transcriptase monomers bound on opposite sides of a pseudo-symmetric non-coding RNA—a 2:1 architecture that could not have been predicted from sequence analysis alone.

Biochemical dissection showed each monomer reverse-transcribes its own side of the template, but only one produces the long repeat product. Which one wins is determined by the distance between two flanking stem-loop anchoring structures. The RNA is not merely a scaffold—it actively specifies which template segment is used for continuous synthesis.

The boundary elements solve a concrete problem: any enzyme that repeatedly copies the same template must know where it starts and ends, or it will drift with each cycle. The stretch of RNA between the stem-loop anchors is the template region fenced in by these two molecular barriers.

🔗 The Surprising Half-Sentence

While working out how DRT10 functions, Tang noticed its mode of operation resembles telomerase—a reverse transcriptase found in organisms evolutionarily very distant from bacteria, including humans.

The similarity might have remained a footnote until Mario Rodríguez Mestre from the University of Copenhagen presented preliminary results of an evolutionary tree of all reverse transcriptases, colored by domain of life: one side almost entirely brown (bacterial enzymes), the other teal (eukaryotic enzymes). On the brown side, one thin teal branch clustered tightly with bacterial reverse transcriptases.

That teal branch was telomerase.

Subsequent analysis placed telomerase and the DRT family in the same monophyletic clade, suggesting their DNA polymerase activity may be homologous. The paper's abstract uses the word *suggesting*.

| Feature | DRT10 | Telomerase | |---|---|---| | Organism | Bacteria | Humans and most eukaryotes | | Reverse transcriptase | Yes | Yes | | Template | Self-encoded non-coding RNA | Self-encoded RNA | | Product | Tandem repeat DNA | Telomeric repeats | | Template boundary | Set by stem-loop anchor spacing | Not described as such in abstract | | Architecture | 2 enzymes + 1 RNA | No corresponding structure in abstract | | Evolutionary relationship | Same monophyletic clade | Same monophyletic clade |

🧬 From Antiviral Defense to Anti-Aging

Sternberg described a concrete test scenario: his lab has already used DRT10 to synthesize human telomeric repeats in human cells and is testing whether chromosome extension can prevent cellular senescence and extend healthspan. Another possible path is CAR-T cell therapy—maintaining and lengthening telomeres to keep therapeutic T cells active longer.

The abstract itself only covers bacterial biochemistry, structure, and phylogeny. Telomere-disease therapy and genome editing applications remain hypotheses until DRT10 is demonstrated to add repeats in eukaryotic cells in a validated setting.

One question remains unanswered: DRT10 adds tandem repeats from its own RNA template. A general editing tool would require proving the RNA template can be swapped for arbitrary sequences. The paper does not address this.

| Editing tool | How it modifies DNA | What it writes | |---|---|---| | CRISPR | Cuts DNA | Nothing—no new sequence written | | Base editors | Swaps one letter | Single base substitution | | DRT10 | Writes using an RNA template | Tandem repeat sequences |

The paper extends its conclusion to the family level: combined with prior work on DRT2, DRT3, and DRT93-5, a conserved mechanistic logic of RNA-templated DNA repeat addition spans diverse DRT systems, despite very different architectural solutions.

The paper went live on *Nature* on October 11, 8:00 PM EDT. First author Stephen Tang; co-first authors Josephine L. Ramirez and Qixiang He; collaborators include Mario Rodríguez Mestre, Tanner Wiegand, Dennis J. Zhang, Megan Wang, George D. Lampe, Jing Wang, Yanzhe Ma, Marko Jovanovic, Rafael Pinilla-Redondo, Israel S. Fernández; corresponding author Samuel H. Sternberg. DOI: 10.1038/s41586-026-11250-8.

🔍 Sources and Caveats

• All mechanistic and structural details come from the Nature abstract page and the Columbia press release; the full text and supplementary materials were not obtained
• The homology conclusion is hedged as *suggesting* in the abstract; common ancestry is limited to DNA polymerase activity—reading it as a settled origin of telomere protection exceeds the abstract's wording
• Sternberg's comments on telomere disease and CAR-T are research directions, not validated results
• Whether the RNA template can be replaced with a custom sequence is unaddressed in the paper and raised here as an open question