Excited to share our new findings in @science.org on how the DRT3 bacterial defense system uses a reverse transcriptase that builds DNA repeats without a nucleic acid template. Microbes never cease to amaze!
www.science.org/doi/10.1126/...
All in all, it’s quite remarkable how creative bacterial defense systems can be! (6/6)
As far as we know, enzymes that make DNA without a nucleic acid template produce sequences that are more or less random (the polyA homopolymer made by DRT9 is RNA-templated). As a result, … (2/6)
Finding that Drt3b uses its own amino acids to produce poly(AC) was quite a surprise. It did not occur to us that second strand synthesis could be performed this way until we saw the cryo-EM structure. (3/6)
But don't rewrite the textbooks! Drt3b is highly tailored for poly(AC) and is NOT a general avenue for amino acid-to-DNA information transfer, though the conceptual implications are fun to consider. (4/6)
Alex Gao
It’s also worth noting that Drt3b has fascinating parallels, as well as mechanistic differences, with nucleotidyltransferases that append sequence-specific tails to RNA, including the CCA-adding enzyme and the poly(UG)-adding RDE-3. These enzymes are structurally quite distinct from RTs. (5/6)
Great summary by @philipcball.bsky.social! Our findings certainly don’t invalidate the central dogma, but rather demonstrate an unexpected (and cool!) structural mechanism by which a sequence-specific DNA is created in a cell. (1/6)
Congratulations to the amazing team of co-first authors @poppy-pujuan-deng.bsky.social, @hyunbinlee0221.bsky.social, and Carlo Armijo!
1/9 New preprint from the Sternberg Lab in collaboration with the Nishimasu Lab! We uncover how the DRT3 antiphage immune system pairs two reverse transcriptases, one RNA-templated and one protein-templated, to build a double-stranded DNA effector. doi.org/10.64898/202...
