Ccr4-Not and TFIIS Function Cooperatively To Rescue Arrested RNA Polymerase II
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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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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).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as 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).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Dutta et al, 2015
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“…have been described: 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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Pulido, V., Rodríguez-Peña, J. M., Alonso, G., Sanz, A. B., Arroyo, J., & García, R. (2024) · Journal of Molecular Biology · doi:10.1016/j.jmb.2024.168570 · Cited by 5 · see citing works
Diverse functions of deadenylases in DNA damage response and genomic integrity
Yan, Y. (2020) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1621 · Cited by 5 · see citing works
Challal, D., Menant, A., Goksal, C., Leroy, E., Al‐Sady, B., & Rougemaille, M. (2023) · Genetics · doi:10.1093/genetics/iyad108 · Cited by 4 · see citing works
Mount, H. O., Urbanus, M. L., Zangari, F., Gingras, A., & Ensminger, A. W. (2024) · mSphere · doi:10.1128/msphere.00891-24 · Cited by 4 · see citing works
FAIR approaches applied to unraveling Plant-Pathogen Interactions Data and RNA Processing Evolution
Iglesias, A. R. (2016) · doi:10.20868/upm.thesis.44220 · Cited by 1 · see citing works
Investigation of NOT1 proteins in regulating gene expression in plasmodium falciparum
Liu, Y. (2019) · doi:10.32657/10220/49669 · Cited by 1 · see citing works
Mount, H. O., Zangari, F., Gingras, A., & Ensminger, A. W. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.06.494580 · Cited by 1 · see citing works
The influence of chromatin in DNA-RNA hybrid metabolism
Martínez, C., & Carlos, J. (2020) · Deposito de Investigacion Universidad de Sevilla (University of Seville)
Ccr4-Not complex reduces transcription efficiency in heterochromatinPreprint
Monteagudo-Mesas, P., Brönner, C., Kohvaei, P., Amedi, H., Canzar, S., & Halić, M. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.08.455218
Liu, M., Li, Y., Yuan, X. H., Rong, S., & Du, J. (2024) · Biochemistry and Cell Biology · doi:10.1139/bcb-2024-0094
Growth rate regulates RNA polymerase II transcription elongation in Saccharomyces cerevisiaePreprint
Garrido-Godino, A. I., González, R., Martín-Expósito, M., Chávez, S., Pérez-Ortín, J. E., & Navarro, F. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.11.26.625403
Growth rate is related to elongation of RNA polymerase II transcription in Saccharomyces cerevisiae
Garrido-Godino, A. I., González, R., Martín‐Expósito, M., Chávez, S., Pérez-Ortín, J. E., & Navarro, F. (2025) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2025.195100
Allen, G. E., Weiss, B., Panasenko, O. O., Huch, S., Villányi, Z., Albert, B., Dilg, D., Zagatti, M., Schaughency, P., Liao, S. E., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22614337
Allen, G. E., Weiss, B., Panasenko, O. O., Huch, S., Villányi, Z., Albert, B., Dilg, D., Zagatti, M., Schaughency, P., Liao, S. E., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22614322
Allen, G. E., Weiss, B., Panasenko, O. O., Huch, S., Villányi, Z., Albert, B., Dilg, D., Zagatti, M., Schaughency, P., Liao, S. E., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22614340
Contrôle de l'expression génique par la RNP 7SK
Studniarek, C. (2019) · theses.fr (ABES) · doi:10.70675/4bab1779z812bz45d6zbcd4z9eea765b52e7
CCR4-NOT is required for suppressing pervasive transcription and retrotransposable elements
Kulkarni, S. D., Morrissey, A., Sebastian, A., Akinniyi, O. T., Keller, C. A., Albert, I. U., Mahony, S., & Reese, J. C. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.113289
Self-citation
- 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
- Publisher
- Informa UK Limited
- Published
- 2015-06-01
- Volume
- 35
- Issue
- 11
- Pages
- 1915-1925
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC4420917
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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