ArticleNucleic acids research2015
Five checkpoints maintaining the fidelity of transcription by RNA polymerases in structural and energetic details.
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 11 papers.
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Who cites it
11 citing papers in PubMed, 30 citations in OpenAlex.
- RNA Polymerase II Activity Control of Gene Expression and Involvement in Disease.Journal of molecular biology · 2025Review
- 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
- Genetic Functionalization of Protein-Based Biomaterials via Protein Fusions.Biomacromolecules · 2024Review
- Characterization of RNA polymerase II trigger loop mutations using molecular dynamics simulations and machine learning.PLoS computational biology · 2023Article
- Transcriptional processing of an unnatural base pair by eukaryotic RNA polymerase II.Nature chemical biology · 2021Article
- Exploring the Minimum-Energy Pathways and Free-Energy Profiles of Enzymatic Reactions with QM/MM Calculations.The journal of physical chemistry. B · 2021Article
- Determining selection free energetics from nucleotide pre-insertion to insertion in viral T7 RNA polymerase transcription fidelity control.Nucleic acids research · 2019Article
- 8-Oxo-guanine DNA damage induces transcription errors by escaping two distinct fidelity control checkpoints of RNA polymerase II.The Journal of biological chemistry · 2019Article
- Kinetics of nucleotide entry into RNA polymerase active site provides mechanism for efficiency and fidelity.Biochimica et biophysica acta. Gene regulatory mechanisms · 2017Article
- Elucidation of the Dynamics of Transcription Elongation by RNA Polymerase II using Kinetic Network Models.Accounts of chemical research · 2016Article
- Bridge helix bending promotes RNA polymerase II backtracking through a critical and conserved threonine residue.Nature communications · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Transcriptional fidelity, which prevents the misincorporation of incorrect nucleoside monophosphates in RNA, is essential for life. Results from molecular dynamics (MD) simulations of eukaryotic RNA polymerase (RNAP) II and bacterial RNAP with experimental data suggest that fidelity may involve as many as five checkpoints. Using MD simulations, the effects of different active site NTPs in both open and closed trigger loop (TL) structures of RNAPs are compared. Unfavorable initial binding of mismatched substrates in the active site with an open TL is proposed to be the first fidelity checkpoint. The leaving of an incorrect substrate is much easier than a correct one energetically from the umbrella sampling simulations. Then, the closing motion of the TL, required for catalysis, is hindered by the presence of mismatched NTPs. Mismatched NTPs also lead to conformational changes in the active site, which perturb the coordination of magnesium ions and likely affect the ability to proceed with catalysis. This step appears to be the most important checkpoint for deoxy-NTP discrimination. Finally, structural perturbations in the template DNA and the nascent RNA in the presence of mismatches likely hinder nucleotide addition and provide the structural foundation for backtracking followed by removing erroneously incorporated nucleotides during proofreading.
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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.