ArticlePLoS genetics2016
High-Resolution Phenotypic Landscape of the RNA Polymerase II Trigger Loop.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed.
- 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
- Sub-2 Å cryo-EM structures of transcribing RNA polymerase II reveal critical roles of water molecules in catalysis.Molecular cell · 2026Article
- Structural basis for multi-subunit DNA-dependent RNA polymerase catalytic activity.Molecular cell · 2026Article
- RNA polymerase inhibitors reveal active-site motions essential for the nucleotide-addition cycle.bioRxiv : the preprint server for biology · 2026Article
- Genetic dissection of transcription start site selection by RNA polymerase II in Saccharomyces cerevisiae.Genetics · 2026Article
- Important role in transcription start site selection for the RNA polymerase II-TFIIE-TFIIH interface in Saccharomyces cerevisiae.Genetics · 2026Article
- RNA polymerase II-TFIIE-TFIIH interface functions in transcription start site selection inbioRxiv : the preprint server for biology · 2025Article
- Genetic dissection of transcription start site selection by RNA Polymerase II inbioRxiv : the preprint server for biology · 2025Article
- Widespread epistasis shapes RNA polymerase II active site function and evolution.Nature communications · 2025Article
- RNA Polymerase II Activity Control of Gene Expression and Involvement in Disease.Journal of molecular biology · 2025Review
- 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
- RNA polymerase SI3 domain modulates global transcriptional pausing and pause-site fluctuations.Nucleic acids research · 2024Article
- Thiolutin has complex effects in vivo but is a direct inhibitor of RNA polymerase II in vitro.Nucleic acids research · 2024Article
- Mutation bias and the predictability of evolution.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Characterization of RNA polymerase II trigger loop mutations using molecular dynamics simulations and machine learning.PLoS computational biology · 2023Article
- On the incongruence of genotype-phenotype and fitness landscapes.PLoS computational biology · 2022Article
- Conserved Trigger Loop Histidine of RNA Polymerase II Functions as a Positional Catalyst Primarily through Steric Effects.Biochemistry · 2021Article
- Mutation bias interacts with composition bias to influence adaptive evolution.PLoS computational biology · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors.
Funding
Abstract
The active sites of multisubunit RNA polymerases have a "trigger loop" (TL) that multitasks in substrate selection, catalysis, and translocation. To dissect the Saccharomyces cerevisiae RNA polymerase II TL at individual-residue resolution, we quantitatively phenotyped nearly all TL single variants en masse. Three mutant classes, revealed by phenotypes linked to transcription defects or various stresses, have distinct distributions among TL residues. We find that mutations disrupting an intra-TL hydrophobic pocket, proposed to provide a mechanism for substrate-triggered TL folding through destabilization of a catalytically inactive TL state, confer phenotypes consistent with pocket disruption and increased catalysis. Furthermore, allele-specific genetic interactions among TL and TL-proximal domain residues support the contribution of the funnel and bridge helices (BH) to TL dynamics. Our structural genetics approach incorporates structural and phenotypic data for high-resolution dissection of transcription mechanisms and their evolution, and is readily applicable to other essential yeast proteins.
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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 Socratic graph.