Cited by 61Genomics and Chromatin DynamicsRNA Research and SplicingNuclear Structure and Function

Ccr4-Not and TFIIS Function Cooperatively To Rescue Arrested RNA Polymerase II

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Dutta, Arnob, Babbarwal, Vinod, Fu, Jianhua, Brunke-Reese, Deborah, Libert, Diane M., Willis, Jonathan, Reese, Joseph C.·2015·Molecular and Cellular Biology

Abstract

Expression of the genome requires RNA polymerase II (RNAPII) to transcribe across many natural and unnatural barriers, and this transcription across barriers is facilitated by protein complexes called elongation factors (EFs). Genetic studies in Saccharomyces cerevisiae yeast suggest that multiple EFs collaborate to assist RNAPII in completing the transcription of genes, but the molecular mechanisms of how they cooperate to promote elongation are not well understood. The Ccr4-Not complex participates in multiple steps of mRNA metabolism and has recently been shown to be an EF. Here we describe how Ccr4-Not and TFIIS cooperate to stimulate elongation. We find that Ccr4-Not and TFIIS mutations show synthetically enhanced phenotypes, and biochemical analyses indicate that Ccr4-Not and TFIIS work synergistically to reactivate arrested RNAPII. Ccr4-Not increases the recruitment of TFIIS into elongation complexes and enhances the cleavage of the displaced transcript in backtracked RNAPII. This is mediated by an interaction between Ccr4-Not and the N terminus of TFIIS. In addition to revealing insights into how these two elongation factors cooperate to promote RNAPII elongation, our study extends the growing body of evidence suggesting that the N terminus of TFIIS acts as a docking/interacting site that allows it to synergize with other EFs to promote RNAPII transcription.

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Crossref · 10.1128/mcb.00044-15

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  • Ccr4-Not can rescue backtracked RNA Pol II in the absence of TFIIS.

    “While Ccr4‐Not can rescue backtracked RNA Pol II in the absence of TFIIS, further in vitro characterization showed that Ccr4‐Not also interacts with TFIIS and recruits it to the arrested elongation complex resulting in enhanced transcript cleavage (Dutta et al, 2015).”
  • Ccr4-Not interacts with TFIIS and recruits it to the arrested elongation complex, resulting in enhanced transcript cleavage.

    “While Ccr4‐Not can rescue backtracked RNA Pol II in the absence of TFIIS, further in vitro characterization showed that Ccr4‐Not also interacts with TFIIS and recruits it to the arrested elongation complex resulting in enhanced transcript cleavage (Dutta et al, 2015).”

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Authors
Dutta, A., Babbarwal, V., Fu, J., Brunke-Reese, D., Libert, D. M., Willis, J., & Reese, J. C.
Affiliations
  • Pennsylvania State University (US)
  • Medical College of Wisconsin (US)
Venue
Molecular and Cellular Biology
Published
2015-06-01
Volume
35
Issue
11
Pages
1915-1925
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2105576664
Cited by
61
References
57
Citations by year
2026: 1 · 2025: 1 · 2024: 5 · 2023: 8 · 2022: 3 · 2021: 4 · 2020: 8 · 2019: 9 · 2018: 3 · 2017: 8 · 2016: 9 · 2015: 2
FWCI
3.19
Type
journal article
Language
en
Open access
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (R01GM100997, GM58672, GM100997, R01GM058672)
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 › Nuclear Structure and Function
Keywords
CCR4-NOT complex, TFIIS, RNA polymerase II, transcription elongation, elongation factors, transcript cleavage, elongation complex, protein-protein interaction, synthetic genetic interactions, Saccharomyces cerevisiae
MeSH terms
Peptide Elongation Factors, Ribonucleases, RNA Polymerase II, RNA, Messenger, Saccharomyces cerevisiae, Transcription, Genetic, Saccharomyces cerevisiae Proteins, Transcriptional Elongation Factors

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