The multifunctional Ccr4–Not complex directly promotes transcription elongation
Open accessAbstract
The Ccr4–Not complex has been implicated in the control of multiple steps of mRNA metabolism; however, its functions in transcription remain ambiguous. The discovery that Ccr4/Pop2 is the major cytoplasmic mRNA deadenylase and the detection of Not proteins within mRNA processing bodies have raised questions about the roles of the Ccr4–Not complex in transcription. Here we firmly establish Ccr4–Not as a positive elongation factor for RNA polymerase II (RNAPII). The Ccr4–Not complex is targeted to the coding region of genes in a transcription-dependent manner similar to RNAPII and promotes elongation in vivo. Furthermore, Ccr4–Not interacts directly with elongating RNAPII complexes and stimulates transcription elongation of arrested polymerase in vitro. Ccr4–Not can reactivate backtracked RNAPII using a mechanism different from that of the well-characterized elongation factor TFIIS. While not essential for its interaction with elongation complexes, Ccr4–Not interacts with the emerging transcript and promotes elongation in a manner dependent on transcript length, although this interaction is not required for it to bind RNAPII. Our comprehensive analysis shows that Ccr4–Not directly regulates transcription, and suggests it does so by promoting the resumption of elongation of arrested RNAPII when it encounters transcriptional blocks in vivo.
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In yeast, genes are quite short (around 1.5-2 kb long on average), although the gene YLR454W used for most experiments measuring RNA Pol II speed in budding yeast is exceptionally large with a size of around 8 kb.
“In yeast, genes are quite short (around 1.5–2 kb long on average, although the gene YLR454W, used for most of the experiments measuring RNA Pol II speed in budding yeast, is exceptionally large with a size of around 8 kb (Table 2) (Mason & Struhl, 2005; Quan & Hartzog, 2010; Kruk et al, 2011; García et al, 2012)).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Kruk et al, 2011
The ‘Ccr4-Not stimulates elongation in vivo’ section uses GAL1p-YLR454W to examine RNA polymerase II progression, with measurements at positions through 6 kb. Our copy does not state that yeast genes average 1.5–2 kb, give YLR454W’s length as approximately 8 kb, or establish that it is used in most budding-yeast polymerase-speed experiments. Page numbers are unavailable in the indexed passages. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe Ccr4-Not complex can accelerate transcription through reactivation of backtracked RNA Pol II.
“Another factor which can accelerate transcription through reactivation of backtracked RNA Pol II is the Ccr4‐Not complex (Kruk et al, 2011), which is considered a master regulator of eukaryotic gene expression.”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Kruk et al, 2011
The Ccr4-Not complex is thought to push RNA Pol II forward through binding to the nascent RNA until realignment of the 3′ end of the nascent transcript in the active site.
“The Ccr4‐Not complex is instead thought to push RNA Pol II forward through binding to the nascent RNA until realignment of the 3′ end of the nascent transcript in the active site (Kruk et al, 2011).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Kruk et al, 2011
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Cites
Longtine, M. S., Mckenzie, A., DeMarini, D. J., Shah, N. G., Wach, A., Brachat, A., Philippsen, P., & Pringle, J. R. (1998) · Yeast · doi:10.1002/(sici)1097-0061(199807)14:10 · Cited by 5,367 · see citing works
Brachmann, C. B., Davies, A., Cost, G. J., Caputo, E. M., Li, J., Hieter, P., & Boeke, J. D. (1998) · Yeast · doi:10.1002/(sici)1097-0061(19980130)14:2 · Cited by 3,411 · see citing works
A generic protein purification method for protein complex characterization and proteome exploration
Rigaut, G., Shevchenko, A., Rutz, B., Wilm, M., Mann, M., & Séraphin, B. (1999) · Nature Biotechnology · doi:10.1038/13732 · Cited by 2,707 · see citing works
P bodies and the control of mRNA translation and degradation
Parker, R., & Sheth, U. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.02.011 · Cited by 1,335 · see citing works
The C-terminal domain of RNA polymerase II couples mRNA processing to transcription
McCracken, S. A., Fong, N., Yankulov, K., Ballantyne, S. M., Pan, G., Greenblatt, J., Patterson, S. D., Wickens, M., & Bentley, D. L. (1997) · Nature · doi:10.1038/385357a0 · Cited by 925 · see citing works
Progression through the RNA Polymerase II CTD Cycle
Buratowski, S. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.10.019 · Cited by 777 · see citing works
Tucker, M., Valencia-Sanchez, M. A., Staples, R. R., Chen, J., Denis, C. L., & Parker, R. (2001) · Cell · doi:10.1016/s0092-8674(01)00225-2 · Cited by 593 · see citing works
Cooperation Between Translating Ribosomes and RNA Polymerase in Transcription Elongation
Proshkin, S., Rahmouni, A. R., Mironov, A. S., & Nudler, E. (2010) · Science · doi:10.1126/science.1184939 · Cited by 565 · see citing works
Rules of engagement: co-transcriptional recruitment of pre-mRNA processing factors
Bentley, D. L. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.04.006 · Cited by 489 · see citing works
Simic, R., Lindstrom, D. L., Tran, H. G., Roinick, K. L., Costa, P. J., Johnson, A. D., Hartzog, G. A., & Arndt, K. M. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg179 · Cited by 368 · see citing works
Distinction and Relationship between Elongation Rate and Processivity of RNA Polymerase II In Vivo
Mason, P. B., & Struhl, K. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.02.017 · Cited by 359 · see citing works
Structure of Eukaryotic RNA Polymerases
Cramer, P., Armache, K., Baumli, S., Benkert, S., Brueckner, F., Buchen, C., Damsma, G. E., Dengl, S., Geiger, S. R., Jasiak, A. J., et al. (2008) · Annual Review of Biophysics · doi:10.1146/annurev.biophys.37.032807.130008 · Cited by 305 · see citing works
Kim, J., Guermah, M., & Roeder, R. G. (2010) · Cell · doi:10.1016/j.cell.2009.12.050 · Cited by 273 · see citing works
Chen, J., Chiang, Y. C., & Denis, C. L. (2002) · The EMBO Journal · doi:10.1093/emboj/21.6.1414 · Cited by 255 · see citing works
Promoting elongation with transcript cleavage stimulatory factors
Fish, R. N., & Kane, C. M. (2002) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(02)00459-1 · Cited by 236 · see citing works
Nature of the Nucleosomal Barrier to RNA Polymerase II
Kireeva, M. L., Hancock, B., Cremona, G. H., Walter, W., Studitsky, V. M., & Kashlev, M. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.02.027 · Cited by 227 · see citing works
Global control of gene expression in yeast by the Ccr4-Not complex
Collart, M. A. (2003) · Gene · doi:10.1016/s0378-1119(03)00672-3 · Cited by 195 · see citing works
The Paf1 Complex Has Functions Independent of Actively Transcribing RNA Polymerase II
Mueller, C. L., Porter, S. E., Hoffman, M. G., et al. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00257-6 · Cited by 194 · see citing works
RSC Exploits Histone Acetylation to Abrogate the Nucleosomal Block to RNA Polymerase II Elongation
Carey, M., Li, B., & Workman, J. L. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.09.012 · Cited by 187 · see citing works
Yeast TAF IIS in a multisubunit complex required for activated transcription
Reese, J. C., Apone, L., Walker, S. S., Griffin, L. A., & Green, M. R. (1994) · Nature · doi:10.1038/371523a0 · Cited by 168 · see citing works
Self-citationRNA Polymerase Active Center: The Molecular Engine of Transcription
Nudler, E. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.052705.164655 · Cited by 168 · see citing works
Missra, A., & Gilmour, D. S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000681107 · Cited by 165 · see citing works
Self-citationChang, M., French-Cornay, D., Fan, H.-Y., Klein, H. L., Denis, C. L., & Jaehning, J. A. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.2.1056 · Cited by 161 · see citing works
Bai, Y., Salvadore, C., Chiang, Y. C., et al. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.10.6642 · Cited by 159 · see citing works
The CCR4–NOT Complex Plays Diverse Roles in mRNA Metabolism
Denis, C. L., & Chen, J. (2003) · Progress in nucleic acid research and molecular biology · doi:10.1016/s0079-6603(03)01007-9 · Cited by 149 · see citing works
The RNA polymerase II subunit Rpb4p mediates decay of a specific class of mRNAsPreprint
Lotan, R., Bar-On, V. G., Harel-Sharvit, L., et al. (2005) · Genes & Development · doi:10.1101/gad.353205 · Cited by 144 · see citing works
A Multiplicity of Coactivators Is Required by Gcn4p at Individual Promoters In Vivo
Swanson, M. J., Qiu, H., Sumibcay, L., Krueger, A., Kim, S., Natarajan, K., Yoon, S., & Hinnebusch, A. G. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.8.2800-2820.2003 · Cited by 142 · see citing works
Zhang, Z., Fu, J., & Gilmour, D. S. (2005) · Genes & Development · doi:10.1101/gad.1296305 · Cited by 138 · see citing works
Self-citationPromoter Proximal Sequences Modulate RNA Polymerase II Elongation by a Novel Mechanism
Reeder, T., & Hawley, D. K. (1996) · Cell · doi:10.1016/s0092-8674(00)81395-1 · Cited by 126 · see citing works
Phatnani, H. P., Jones, J. C., & Greenleaf, A. L. (2004) · Biochemistry · doi:10.1021/bi048364h · Cited by 123 · see citing works
Collart, M. A., & Timmers, H. T. M. (2004) · Progress in nucleic acid research and molecular biology · doi:10.1016/s0079-6603(04)77008-7 · Cited by 122 · see citing works
Panasenko, O. O., Landrieux, E., Feuermann, M., Finka, A., Paquet, N., & Collart, M. A. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604986200 · Cited by 110 · see citing works
Polyubiquitination of the demethylase Jhd2 controls histone methylation and gene expressionPreprint
Mersman, D. P., Du, H., Fingerman, I. M., South, P. F., & Briggs, S. D. (2009) · Genes & Development · doi:10.1101/gad.1769209 · Cited by 109 · see citing works
RNA emerging from the active site of RNA polymerase II interacts with the Rpb7 subunit
Újvári, A., & Luse, D. S. (2005) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1026 · Cited by 108 · see citing works
Single-molecule tracking of mRNA exiting from RNA polymerase II
Andrecka, J., Lewis, R., Brückner, F., Lehmann, E., Cramer, P., & Michaelis, J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703815105 · Cited by 108 · see citing works
Kim, B., Nesvizhskii, A. I., Rani, P. G., Hahn, S., Aebersold, R. H., & Ranish, J. A. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704573104 · Cited by 108 · see citing works
Contending with transcriptional arrest during RNAPII transcript elongation
Svejstrup, J. Q. (2007) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2007.02.005 · Cited by 107 · see citing works
RNA Polymerase Elongation Factors
Roberts, J. W., Shankar, S., & Filter, J. J. (2008) · Annual Review of Microbiology · doi:10.1146/annurev.micro.61.080706.093422 · Cited by 105 · see citing works
CCR4/NOT complex associates with the proteasome and regulates histone methylation
Laribee, R., Shibata, Y., Mersman, D. P., Collins, S. R., Kemmeren, P., Roguev, A., Weissman, J., Briggs, S. D., Krogan, N., & Strahl, B. (2007) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0607996104 · Cited by 101 · see citing works
Desmoucelles, C., Pinson, B., Saint‐Marc, C., & Daignan‐Fornier, B. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111433200 · Cited by 97 · see citing works
Qiu, H., Hu, C., Yoon, S., Natarajan, K., Swanson, M. J., & Hinnebusch, A. G. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.10.4104-4117.2004 · Cited by 94 · see citing works
Sharma, V. M., Tomar, R. S., Dempsey, A., & Reese, J. C. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.02311-06 · Cited by 94 · see citing works
Self-citationGaillard, H., Tous, C., Botet, J., González‐Aguilera, C., Quintero, M., Viladevall, L., García-Rubio, M. L., Rodríguez‐Gil, A., Marín, A., Ariño, J., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000364 · Cited by 93 · see citing works
Maillet, L., & Collart, M. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m107979200 · Cited by 92 · see citing works
Genetic Evidence Supports a Role for the Yeast CCR4-NOT Complex in Transcriptional Elongation
Denis, C. L., Chiang, Y. C., Cui, Y., & Chen, J. (2001) · Genetics · doi:10.1093/genetics/158.2.627 · Cited by 85 · see citing works
Badarinarayana, V., Chiang, Y. C., & Denis, C. L. (2000) · Genetics · doi:10.1093/genetics/155.3.1045 · Cited by 84 · see citing works
Regulation of histone H3K4 tri-methylation and PAF complex recruitment by the Ccr4-Not complex
Mulder, K. W., Brenkman, A. B., Inagaki, A., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm175 · Cited by 80 · see citing works
Runner, V. M., Podolny, V., & Buratowski, S. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01714-07 · Cited by 79 · see citing works
Riles, L., Shaw, R. J., Johnston, M., & Reines, D. (2004) · Yeast · doi:10.1002/yea.1068 · Cited by 77 · see citing works
Mulder, K. W. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki938 · Cited by 73 · see citing works
Genetic Interactions between TFIIS and the Swi-Snf Chromatin-Remodeling Complex
Davie, J. K., & Kane, C. M. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.16.5960-5973.2000 · Cited by 72 · see citing works
The Ccr4-Not Complex and yTAF1 (yTaf II 130p/yTaf II 145p) Show Physical and Functional Interactions
Deluen, C., James, N., Maillet, L., et al. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.19.6735-6749.2002 · Cited by 71 · see citing works
Dedrick, R. L., & Chamberlin, M. J. (1985) · Biochemistry · doi:10.1021/bi00330a019 · Cited by 68 · see citing works
The CCR4-NOT Complex Physically and Functionally Interacts with TRAMP and the Nuclear Exosome
Azzouz, N., Panasenko, O. O., Colau, G., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006760 · Cited by 63 · see citing works
Running with RNA polymerase: eukaryotic transcript elongation
Arndt, K. M., & Kane, C. M. (2003) · Trends in Genetics · doi:10.1016/j.tig.2003.08.008 · Cited by 54 · see citing works
Mulder, K. W., Inagaki, A., Cameroni, E., Mousson, F., Winkler, G. S., VIRGILIO, C. D., Collart, M. A., & Timmers, H. T. M. (2007) · Genetics · doi:10.1534/genetics.106.060640 · Cited by 54 · see citing works
Morillo‐Huesca, M., Vanti, M., & Chávez, S. (2006) · FEBS Journal · doi:10.1111/j.1742-4658.2005.05108.x · Cited by 51 · see citing works
Pillai, B., Sampath, V., Sharma, N., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010952200 · Cited by 41 · see citing works
Zhang, Z., & Reese, J. C. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.17.7399-7411.2005 · Cited by 37 · see citing works
Self-citationYeast Rap1 contributes to genomic integrity by activating DNA damage repair genes
Tomar, R. S., Zheng, S., Brunke-Reese, D., Wolcott, H. N., & Reese, J. C. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.93 · Cited by 33 · see citing works
Self-citationSuh, M.-H., Ye, P., Zhang, M., Hausmann, S., Shuman, S., Gnatt, A. L., & Fu, J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507987102 · Cited by 28 · see citing works
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RNA polymerase II speed: a key player in controlling and adapting transcriptome composition
Muniz, L., Nicolas, E., & Trouche, D. (2021) · The EMBO Journal · doi:10.15252/embj.2020105740 · Cited by 203 · see citing works
“…genes are quite short (around 1.5 – 2 kb long on average, although the gene YLR454W, used for most of the experiments measuring RNA Pol II speed in budding yeast, is exceptionally large with a size of around 8 kb (Table 2) (Mason & Struhl, 2005; Quan & Hartzog, 2010; Kruk et al , 2011; Garc (cid”
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Dutta, A., Babbarwal, V., Fu, J., Brunke-Reese, D., Libert, D. M., Willis, J., & Reese, J. C. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00044-15 · Cited by 61 · see citing works
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- Authors
- Kruk, J. A., Dutta, A., Fu, J., Gilmour, D. S., & Reese, J. C.
- Affiliations
- Pennsylvania State University (US)
- Medical College of Wisconsin (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2011-03-15
- Volume
- 25
- Issue
- 6
- Pages
- 581-593
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC3059832
- OpenAlex
- W2138461551
- Cited by
- 177
- References
- 61
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 13 · 2023: 17 · 2022: 6 · 2021: 14 · 2020: 11 · 2019: 13 · 2018: 4 · 2017: 13 · 2016: 15 · 2015: 8 · 2014: 8 · 2013: 18 · 2012: 17
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM047477, GM 47477, R01GM100997, GM58672, 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, transcription elongation, RNA polymerase II, elongation arrest
- MeSH terms
- Protein Binding, RNA Polymerase II, Saccharomyces cerevisiae, Transcription Factors, Gene Expression Regulation, Fungal, Transcriptional Elongation Factors
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