ArticleNucleic acids research2015
Backtracking behavior in viral RNA-dependent RNA polymerase provides the basis for a second initiation site.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 44 citations in OpenAlex.
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- The nucleoside analog CMX521 inhibits coronavirus RNA-dependent RNA polymerase via a two-pronged mechanism.bioRxiv : the preprint server for biology · 2026Article
- Copy-back RNA synthesis by coronavirus polymerase requires helicase activity and is stimulated by remdesivir and molnupiravir.Science advances · 2026Article
- Template switching by coronavirus polymerase requires helicase activity and is stimulated by remdesivir and molnupiravir.bioRxiv : the preprint server for biology · 2025Article
- Programmable self-replicating JEV nanotherapeutics redefine RNA delivery in ALS.Communications biology · 2025Review
- A post-assembly conformational change makes the SARS-CoV-2 polymerase elongation-competent.Nucleic acids research · 2025Article
- Identification of consensus hairpin loop structure among the negative sense subgenomic RNAs of SARS-CoV-2.Bulletin of the National Research Centre · 2023Article
- Characterizing single-molecule dynamics of viral RNA-dependent RNA polymerases with multiplexed magnetic tweezers.STAR protocols · 2022Article
- RNA polymerization actuating nucleic acid membrane (RANAM)-based biosensing for universal RNA virus detection.Biosensors & bioelectronics · 2022Article
- Druggable targets and therapeutic development for COVID-19.Frontiers in chemistry · 2022Review
- Structures and functions of coronavirus replication-transcription complexes and their relevance for SARS-CoV-2 drug design.Nature reviews. Molecular cell biology · 2022Review
- Force spectroscopy with electromagnetic tweezers.Journal of applied physics · 2021Article
- Inhibition of SARS-CoV-2 polymerase by nucleotide analogs from a single-molecule perspective.eLife · 2021Article
- The nucleotide addition cycle of the SARS-CoV-2 polymerase.Cell reports · 2021Article
- Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Inhibition of SARS-CoV-2 polymerase by nucleotide analogs: a single molecule perspective.bioRxiv : the preprint server for biology · 2021Article
- The nucleotide addition cycle of the SARS-CoV-2 polymerase.bioRxiv : the preprint server for biology · 2021Article
- Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex.bioRxiv : the preprint server for biology · 2021Article
- Evolutionary history of cotranscriptional editing in the paramyxoviral phosphoprotein gene.Virus evolution · 2021Review
- Targeting the RdRp of Emerging RNA Viruses: The Structure-Based Drug Design Challenge.Molecules (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Transcription in RNA viruses is highly dynamic, with a variety of pauses interrupting nucleotide addition by RNA-dependent RNA polymerase (RdRp). For example, rare but lengthy pauses (>20 s) have been linked to backtracking for viral single-subunit RdRps. However, while such backtracking has been well characterized for multi-subunit RNA polymerases (RNAPs) from bacteria and yeast, little is known about the details of viral RdRp backtracking and its biological roles. Using high-throughput magnetic tweezers, we quantify the backtracking by RdRp from the double-stranded (ds) RNA bacteriophage Φ6, a model system for RdRps. We characterize the probability of entering long backtracks as a function of force and propose a model in which the bias toward backtracking is determined by the base paring at the dsRNA fork. We further discover that extensive backtracking provides access to a new 3'-end that allows for the de novo initiation of a second RdRp. This previously unidentified behavior provides a new mechanism for rapid RNA synthesis using coupled RdRps and hints at a possible regulatory pathway for gene expression during viral RNA transcription.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.