ArticleProceedings of the National Academy of Sciences of the United States of America2016
Mechanisms of backtrack recovery by RNA polymerases I and II.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 120 citations in OpenAlex.
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- The A12.2 Subunit Plays an Integral Role in Pyrophosphate Release of RNA Polymerase I.Journal of molecular biology · 2023Article
- Regulation of ribosomal RNA gene copy number, transcription and nucleolus organization in eukaryotes.Nature reviews. Molecular cell biology · 2023Review
- Transient-State Kinetic Analysis of the RNA Polymerase II Nucleotide Incorporation Mechanism.Biochemistry · 2023Article
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- Uncovering the mechanisms of transcription elongation by eukaryotic RNA polymerases I, II, and III.iScience · 2022Article
- The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans.Life science alliance · 2022Article
- Optical tweezers across scales in cell biology.Trends in cell biology · 2022Review
- RNA polymerase I (Pol I) lobe-binding subunit Rpa12.2 promotes RNA cleavage and proofreading.The Journal of biological chemistry · 2022Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
During DNA transcription, RNA polymerases often adopt inactive backtracked states. Recovery from backtracks can occur by 1D diffusion or cleavage of backtracked RNA, but how polymerases make this choice is unknown. Here, we use single-molecule optical tweezers experiments and stochastic theory to show that the choice of a backtrack recovery mechanism is determined by a kinetic competition between 1D diffusion and RNA cleavage. Notably, RNA polymerase I (Pol I) and Pol II recover from shallow backtracks by 1D diffusion, use RNA cleavage to recover from intermediary depths, and are unable to recover from extensive backtracks. Furthermore, Pol I and Pol II use distinct mechanisms to avoid nonrecoverable backtracking. Pol I is protected by its subunit A12.2, which decreases the rate of 1D diffusion and enables transcript cleavage up to 20 nt. In contrast, Pol II is fully protected through association with the cleavage stimulatory factor TFIIS, which enables rapid recovery from any depth by RNA cleavage. Taken together, we identify distinct backtrack recovery strategies of Pol I and Pol II, shedding light on the evolution of cellular functions of these key enzymes.
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