Evidence map›Paper›PMID 22509745›Full record

ArticleJournal of the American Chemical Society2012

Dissecting chemical interactions governing RNA polymerase II transcriptional fidelity.

Matthew W Kellinger, Sébastien Ulrich, Jenny Chong, Eric T Kool, Dong Wang

Abstract read
In one paragraph

Article in Journal of the American Chemical Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing 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

24 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Structural basis of transcriptional stalling and bypass of abasic DNA lesion by RNA polymerase II.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  7. Epigenetic DNA Modification NJournal of the American Chemical Society · 2017
    Article
  8. The mChemical science · 2017
    Article
  9. Mechanism of DNA alkylation-induced transcriptional stalling, lesion bypass, and mutagenesis.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  10. Article
  11. RNA polymerase II senses obstruction in the DNA minor groove via a conserved sensor motif.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Strand-specific (asymmetric) contribution of phosphodiester linkages on RNA polymerase II transcriptional efficiency and fidelity.Proceedings of the National Academy of Sciences of the United States of America · 2014
    Article
  18. Review
  19. Article
  20. Article
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

5 authors.

Matthew W KellingerSkaggs School of Pharmacy and Pharmaceutical Sciences, The University of California, San Diego, La Jolla, California 92093-0625, United States.
Sébastien Ulrich
Jenny Chong
Eric T Kool
Dong Wang

Funding

Probing Nucleotide Recognition in the Genetic Information PathwayR01GM072705 · NIGMS · STANFORD UNIVERSITY · PI KOOL, ERIC T. · 2004 to 2012
$2.4M
Structural Basis of Transcriptional Mutagenesis and Arrest of RNA Polymerase IIR00GM085136 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WANG, DONG · 2010 to 2012
$742k
Structural Basis of Transcriptional Mutagenesis and Arrest of RNA Polymerase IIK99GM085136 · NIGMS · STANFORD UNIVERSITY · PI WANG, DONG · 2008 to 2009
$180k
NIGMS NIH HHS GM072705NIGMS NIH HHS GM085136NIGMS NIH HHS K99 GM085136NIGMS NIH HHS R00 GM085136NIGMS NIH HHS R01 GM072705
6 · The paper itself

Abstract

Maintaining high transcriptional fidelity is essential to life. For all eukaryotic organisms, RNA polymerase II (Pol II) is responsible for messenger RNA synthesis from the DNA template. Three key checkpoint steps are important in controlling Pol II transcriptional fidelity: nucleotide selection and incorporation, RNA transcript extension, and proofreading. Some types of DNA damage significantly reduce transcriptional fidelity. However, the chemical interactions governing each individual checkpoint step of Pol II transcriptional fidelity and the molecular basis of how subtle DNA base damage leads to significant losses of transcriptional fidelity are not fully understood. Here we use a series of "hydrogen bond deficient" nucleoside analogues to dissect chemical interactions governing Pol II transcriptional fidelity. We find that whereas hydrogen bonds between a Watson-Crick base pair of template DNA and incoming NTP are critical for efficient incorporation, they are not required for efficient transcript extension from this matched 3'-RNA end. In sharp contrast, the fidelity of extension is strongly dependent on the discrimination of an incorrect pattern of hydrogen bonds. We show that U:T wobble base interactions are critical to prevent extension of this mismatch by Pol II. Additionally, both hydrogen bonding and base stacking play important roles in controlling Pol II proofreading activity. Strong base stacking at the 3'-RNA terminus can compensate for loss of hydrogen bonds. Finally, we show that Pol II can distinguish very subtle size differences in template bases. The current work provides the first systematic evaluation of electrostatic and steric effects in controlling Pol II transcriptional fidelity.

Indexed as

Transcription, GeneticBase SequenceDNAHydrogen BondingModels, MolecularProtein ConformationRNA Polymerase IISaccharomyces cerevisiaeThymineDNARNA Polymerase IIThymine

Identifiers

PMID22509745
PMCPMC3367139

What OpenQuestion holds

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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.