Evidence map›Paper›PMID 18538653›Full record

ArticleMolecular cell2008

The RNA polymerase II trigger loop functions in substrate selection and is directly targeted by alpha-amanitin.

Craig D Kaplan, Karl-Magnus Larsson, Roger D Kornberg

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers.

0numbers the graph read from it
0cells of the map it votes in
172citing papers in PubMed
9.9field-weighted citation impact, top 2% of its field
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

172 citing papers in PubMed, 258 citations in OpenAlex.

  1. Article
  2. 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 · 2026
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  12. Review
  13. International journal of molecular sciences · 2024
    Review
  14. Article
  15. Higher-order epistasis within Pol II trigger loop haplotypes.bioRxiv : the preprint server for biology · 2024
    Article
  16. 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 · 2024
    Article
  17. Article
  18. Review
  19. Article
  20. Article

112 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Craig D KaplanDepartment of Structural Biology, Stanford University, Stanford, CA 94305, USA. cdkaplan@stanford.edu
Karl-Magnus Larsson
Roger D Kornberg
Stanford University · US

Funding

Structure of the Eukaryote Transcription ApparatusR01AI021144 · NIAID · STANFORD UNIVERSITY · PI KORNBERG, ROGER D · 1985 to 2018
$10.3M
STRUCTURE OF RNA POLYMERASE IIR01GM049985 · NIGMS · STANFORD UNIVERSITY · PI PUGLISI, JOSEPH D · 1993 to 2020
$10.2M
TUMOR BIOLOGYT32CA009151 · NCI · STANFORD UNIVERSITY · PI CLEARY, MICHAEL L · 1985 to 2014
$5.5M
RNA POLYMERASE II TRANSCRIPTION SYSTEM FROM YEASTR01GM036659 · NIGMS · STANFORD UNIVERSITY · PI KORNBERG, ROGER D · 1986 to 2016
$4.7M
RNA POLYMERASE II TRANSCRIPTION SYSTEM FROM YEASTR37GM036659 · NIGMS · STANFORD UNIVERSITY · PI KORNBERG, ROGER D · 1998 to 2008
$4.6M
Biochemical analysis of Pol II elongation complexes and mechanismF32GM077787 · NIGMS · STANFORD UNIVERSITY · PI KAPLAN, CRAIG D · 2007 to 2007
$53k
NCI NIH HHS T32 CA009151NIAID NIH HHS R01 AI021144NIGMS NIH HHS F32 GM077787NIGMS NIH HHS GM36659NIGMS NIH HHS GM49985NIGMS NIH HHS R01 GM036659NIGMS NIH HHS R01 GM049985NIGMS NIH HHS R37 GM036659
6 · The paper itself

Abstract

Structural, biochemical, and genetic studies have led to proposals that a mobile element of multisubunit RNA polymerases, the Trigger Loop (TL), plays a critical role in catalysis and can be targeted by antibiotic inhibitors. Here we present evidence that the Saccharomyces cerevisiae RNA Polymerase II (Pol II) TL participates in substrate selection. Amino acid substitutions within the Pol II TL preferentially alter substrate usage and enzyme fidelity, as does inhibition of transcription by alpha-amanitin. Finally, substitution of His1085 in the TL specifically renders Pol II highly resistant to alpha-amanitin, indicating a functional interaction between His1085 and alpha-amanitin that is supported by rerefinement of an alpha-amanitin-Pol II crystal structure. We propose that alpha-amanitin-inhibited Pol II elongation, which is slow and exhibits reduced substrate selectivity, results from direct alpha-amanitin interference with the TL.

Indexed as

Alpha-AmanitinAmino Acid SubstitutionDNA Transposable ElementsDrug Resistance, FungalHistidineMutationNucleic Acid Synthesis InhibitorsPhenotypeRNA Polymerase IISaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSubstrate SpecificityTranscription, GeneticAlpha-AmanitinDNA Transposable ElementsHistidineNucleic Acid Synthesis InhibitorsRNA Polymerase IIRPB1 protein, S cerevisiaeSaccharomyces cerevisiae Proteins

Identifiers

PMID18538653
PMCPMC2475549
OpenAlexW2141325621

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.