Pause & go: from the discovery of RNA polymerase pausing to its functional implications

Mayer, Andreas; Landry, Heather M; Churchman, L Stirling

doi:10.1016/j.ceb.2017.03.002

Cited by 125Genomics and Chromatin DynamicsRNA Research and SplicingRNA and protein synthesis mechanisms

Pause & go: from the discovery of RNA polymerase pausing to its functional implications

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Mayer, Andreas, Landry, Heather M, Churchman, L Stirling·2017·Current Opinion in Cell Biology

DOI 10.1016/j.ceb.2017.03.002PMC PMC5505790

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Abstract

The synthesis of nascent RNA is a discontinuous process in which phases of productive elongation by RNA polymerase are interrupted by frequent pauses. Transcriptional pausing was first observed decades ago, but was long considered to be a special feature of transcription at certain genes. This view was challenged when studies using genome-wide approaches revealed that RNA polymerase II pauses at promoter-proximal regions in large sets of genes in Drosophila and mammalian cells. High-resolution genomic methods uncovered that pausing is not restricted to promoters, but occurs globally throughout gene-body regions, implying the existence of key-rate limiting steps in nascent RNA synthesis downstream of transcription initiation. Here, we outline the experimental breakthroughs that led to the discovery of pervasive transcriptional pausing, discuss its emerging roles and regulation, and highlight the importance of pausing in human development and disease.

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Transcription elongation is frequently interrupted by pauses induced by roadblocks such as nucleosomes, DNA-binding proteins, or mis-incorporated nucleotides, which can affect the average speed of transcription.
“Indeed, transcription elongation is frequently interrupted by pauses induced by roadblocks such as nucleosomes, DNA‐binding proteins, or mis‐incorporated nucleotides (Mayer et al, 2017), which can thus affect the average speed of transcription.”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Mayer et al, 2017
The Introduction describes frequent pauses during elongation, and “Causes of RNA polymerase pausing” identifies nucleosomes and DNA-binding proteins as barriers that induce pausing. That section also links histone depletion to faster elongation. Our copy does not establish mis-incorporated nucleotides as a cause of pausing, so that example is unsupported. (LLM, conf=0.85)
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Authors: Mayer, A., Landry, H. M., & Churchman, L. S.
Affiliations: Harvard University (US)
Corresponding author: Churchman, L Stirling
ORCID: Mayer, Andreas
Churchman, L Stirling
Venue: Current Opinion in Cell Biology
Publisher: Elsevier BV
Published: 2017-06
Volume: 46
Pages: 72-80
ISSN: 0955-0674 (ISSN-L)
DOI: 10.1016/j.ceb.2017.03.002
PMC: PMC5505790
OpenAlex: W2598811737
Cited by: 125
References: 136
Citations by year: 2026: 9 · 2025: 4 · 2024: 10 · 2023: 21 · 2022: 10 · 2021: 18 · 2020: 18 · 2019: 19 · 2018: 11 · 2017: 5
FWCI: 1.36
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Current Opinion in Cell Biology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
Funders: US National Institutes of Health National Human Genome Research Institute (NHGRI) (R01HG007173)
National Institutes of General Medical Science (NIGMS) (R01GM117333)
Long-Term Postdoctoral Fellowships (LT000314/2013-L)
European Molecular Biology Organization (ALTF858-2012)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords: RNA polymerase pausing, transcriptional pausing, RNA polymerase II, promoter-proximal pausing, transcription elongation, human development, disease
MeSH terms: Animals, Gene Expression Regulation, Humans, Promoter Regions, Genetic, RNA Polymerase II, DNA-Directed RNA Polymerases, Transcription, Genetic, Genome, Sequence Analysis, RNA, Transcription Elongation, Genetic

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Pause & go: from the discovery of RNA polymerase pausing to its functional implications

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