Defense-associated reverse transcriptases define an emerging class of noncanonical DNA-writing systems

Defense-associated reverse transcriptases (DRTs) are emerging as a mechanistically diverse class of bacterial antiviral enzymes. Rather than acting simply as RNA-to-DNA copying proteins, they generate a wide range of unconventional DNA products, including de novo gene-assembling cDNAs, random single-stranded DNA, DNA homopolymers, poly(A)-rich cDNAs and protein-templated dinucleotide-repeat DNA. These findings suggest that DRTs are better viewed as DNA-construction modules than as unusual versions of canonical reverse transcriptases. In particular, DRT3 shows how RNA-templated and protein-templated synthesis can be combined within a single defence pathway to generate complementary repeat strands and repeat double-stranded DNA. We argue that this emerging chemistry expands the landscape of prokaryotic reverse transcription and may offer new reaction principles for synthetic biology and nucleic acid engineering.