Speaker: Sam Sternberg, Howard Hughes Medical Institute at Columbia University
Host: Ryo Morimoto, Department of Molecular Biology
Bacteria deploy diverse antiviral systems to defend against foreign pathogens, including CRISPR–Cas nucleases that use guide RNAs to target DNA cleavage, establishing RNA-guided immunity as a central paradigm. Our recent work uncovered a complementary strategy: defense-associated reverse transcriptases (DRTs) that use template RNAs to direct DNA synthesis during phage infection. DRT2 and DRT9 systems generate distinct DNA products — de novo genes and toxic homopolymers through unconventional reverse transcription mechanisms. More recently, we identified DRT10, which catalyzes protein-primed, RNA-templated synthesis of tandem-repeat DNA via a structured ncRNA. This repeat addition mechanism closely parallels telomerase, with shared requirements for template boundary definition and iterative realignment during DNA synthesis. Phylogenetic and structural analyses suggest that telomerase evolved from bacterial DRT-like enzymes, revealing an unexpected evolutionary link between antiviral immunity and eukaryotic chromosome maintenance. Together, these findings expand RNA-guided immunity beyond CRISPR and establish reverse transcription as a broadly conserved strategy for nucleic acid-based defense.