ArticleProceedings of the National Academy of Sciences of the United States of America2012
Trigger loop dynamics mediate the balance between the transcriptional fidelity and speed of RNA polymerase II.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 144 citations in OpenAlex.
- A-to-I mRNA editing: Why not simply incorporate inosine during mRNA synthesis?Molecular biology reports · 2026Review
- Structural dynamics of RNA polymerase II throughout the nucleotide addition cycle.Nature communications · 2026Article
- RNA polymerase inhibitors reveal active-site motions essential for the nucleotide addition cycle.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Structural Dynamics of RNA Polymerase II During Nucleotide Addition Cycle.bioRxiv : the preprint server for biology · 2026Article
- Sub-2 Å cryo-EM structures of transcribing RNA polymerase II reveal critical roles of water molecules in catalysis.Molecular cell · 2026Article
- RNA polymerase inhibitors reveal active-site motions essential for the nucleotide-addition cycle.bioRxiv : the preprint server for biology · 2026Article
- Widespread epistasis shapes RNA polymerase II active site function and evolution.Nature communications · 2025Article
- A narrow range of transcript-error rates across the Tree of Life.Science advances · 2025Article
- FACT weakens the nucleosomal barrier to transcription and preserves its integrity by forming a hexasome-like intermediate.Molecular cell · 2025Article
- RNA Polymerase II Activity Control of Gene Expression and Involvement in Disease.Journal of molecular biology · 2025Review
- NTPs compete in the active site of RNA polymerases I and II.Biophysical chemistry · 2024Article
- Article
- Higher-order epistasis within Pol II trigger loop haplotypes.bioRxiv : the preprint server for biology · 2024Article
- Structural basis of transcription: RNA polymerase II substrate binding and metal coordination using a free-electron laser.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Reversible Kinetics in Multi-nucleotide Addition Catalyzed by S. cerevisiae RNA polymerase II Reveal Slow Pyrophosphate Release.Journal of molecular biology · 2024Article
- RNA polymerase SI3 domain modulates global transcriptional pausing and pause-site fluctuations.Nucleic acids research · 2024Article
- Article
- Characterization of RNA polymerase II trigger loop mutations using molecular dynamics simulations and machine learning.PLoS computational biology · 2023Article
- Transient-State Kinetic Analysis of the RNA Polymerase II Nucleotide Incorporation Mechanism.Biochemistry · 2023Article
- Uncovering the mechanisms of transcription elongation by eukaryotic RNA polymerases I, II, and III.iScience · 2022Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
During transcription, RNA polymerase II (RNAPII) must select the correct nucleotide, catalyze its addition to the growing RNA transcript, and move stepwise along the DNA until a gene is fully transcribed. In all kingdoms of life, transcription must be finely tuned to ensure an appropriate balance between fidelity and speed. Here, we used an optical-trapping assay with high spatiotemporal resolution to probe directly the motion of individual RNAPII molecules as they pass through each of the enzymatic steps of transcript elongation. We report direct evidence that the RNAPII trigger loop, an evolutionarily conserved protein subdomain, serves as a master regulator of transcription, affecting each of the three main phases of elongation, namely: substrate selection, translocation, and catalysis. Global fits to the force-velocity relationships of RNAPII and its trigger loop mutants support a Brownian ratchet model for elongation, where the incoming NTP is able to bind in either the pre- or posttranslocated state, and movement between these two states is governed by the trigger loop. Comparison of the kinetics of pausing by WT and mutant RNAPII under conditions that promote base misincorporation indicate that the trigger loop governs fidelity in substrate selection and mismatch recognition, and thereby controls aspects of both transcriptional accuracy and rate.
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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.