DNA replication complexes (replisomes) routinely encounter proteins and unusual nucleic acid structures that can impede their progress. Barriers can include transcription complexes and R‐loops that form when RNA hybridizes with complementary DNA templates behind RNA polymerases. Cells encode several RNA polymerase and R‐loop clearance mechanisms to limit replisome exposure to these potential obstructions. One such mechanism is hydrolysis of R‐loops by ribonuclease HI (RNase HI). Here, we examine the cellular role of the interaction between
Transcription polymerase–catalyzed emergence of novel RNA replicons
Transcription polymerases can exhibit an unusual mode of regenerating certain RNA templates from RNA, yielding systems that can replicate and evolve with RNA as the information carrier. Two classes of pathogenic RNAs (hepatitis delta virus in animals and viroids in plants) are copied by host transcription polymerases. Using in vitro RNA replication by the transcription polymerase of T7 bacteriophage as an experimental model, we identify hundreds of new replicating RNAs, define three mechanistic hallmarks of replication (subterminal de novo initiation, RNA shape-shifting, and interrupted rolling-circle synthesis), and describe emergence from DNA seeds as a mechanism for the origin of novel RNA replicons. These results inform models for the origins and replication of naturally occurring RNA genetic elements and suggest a means by which diverse RNA populations could be propagated as hereditary material in cellular contexts.
more » « less- NSF-PAR ID:
- 10143810
- Publisher / Repository:
- American Association for the Advancement of Science (AAAS)
- Date Published:
- Journal Name:
- Science
- Volume:
- 368
- Issue:
- 6487
- ISSN:
- 0036-8075
- Page Range / eLocation ID:
- Article No. eaay0688
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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