Evidence map›Paper›PMID 40866334›Full record

ArticleNature communications2025

Widespread epistasis shapes RNA polymerase II active site function and evolution.

Bingbing Duan, Chenxi Qiu, Sing-Hoi Sze, Craig Kaplan

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Higher-order epistasis within Pol II trigger loop haplotypes.bioRxiv : the preprint server for biology · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Bingbing DuanDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-3645-0700
Chenxi QiuDepartment of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Sing-Hoi SzeDepartment of Computer Science and Engineering, Texas A&M University, College Station, TX, USA.
Craig KaplanDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA. craig.kaplan@pitt.edu.ORCID http://orcid.org/0000-0002-7518-695X

Funding

Mechanisms of RNA Polymerase II transcriptionR35GM144116 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Craig Kaplan · 2022 to 2026
$3.4M
Mechanism and Regulation of RNA Polymerase II ElongationR01GM097260 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KAPLAN, CRAIG · 2011 to 2020
$3.3M
High-Throughput Computing for Genomics and Bioinformatics ResearchS10OD028483 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEE, ADRIAN V · 2021 to 2021
$574k
NIGMS NIH HHS R01 GM097260NIGMS NIH HHS R35 GM144116NIH HHS S10 OD028483U.S. Department of Health & Human Services | National Institutes of Health (NIH) S10OD028483U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01GM097260U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM144116
6 · The paper itself

Abstract

Multi-subunit RNA Polymerases are responsible for transcription in all kingdoms of life. These enzymes rely on dynamic, highly conserved active site domains such as the so-called "trigger loop" to accomplish steps in the transcription cycle. Mutations in the RNA polymerase II trigger loop confer a spectrum of biochemical and genetic phenotypes that suggest two main classes, which decrease or increase catalysis or other nucleotide addition cycle events. The RNA polymerase II active site relies on networks of residue interactions to function, and mutations likely perturb these networks in ways that may alter mechanisms. Here, we take a structural genetics approach to reveal residue interactions within and surrounding the RNA polymerase II trigger loop - determining its "interaction landscape" - by deep mutational scanning in Saccharomyces cerevisiae RNA polymerase II. This analysis reveals connections between trigger loop residues and surrounding domains, demonstrating that trigger loop function is tightly coupled to its specific enzyme context.

Indexed as

Epistasis, GeneticEvolution, MolecularRNA Polymerase IISaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsCatalytic DomainModels, MolecularMutationTranscription, GeneticRNA Polymerase IISaccharomyces cerevisiae Proteins

Identifiers

PMID40866334
PMCPMC12391331

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.