Biology:CCR4-Not

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Short description: Multiprotein complex used in gene expression
Structure of human CNOT1-CNOT2-CNOT3 module (PDB 4C0D).[1]

Carbon Catabolite Repression—Negative On TATA-less, or CCR4-Not, is a multiprotein complex that functions in gene expression.[2][3] The complex has multiple enzymatic activities as both a poly(A) 3′-5′ exonuclease and a ubiquitin ligase.[4][5][6][7] The exonuclease activity of CCR4-Not shortens the poly(A) tail found at 3' end of almost every eukaryotic mRNA.[8] The complex is present both in the nucleus where it regulates transcription and in the cytoplasm where it associates with translating ribosomes and RNA processing bodies.[2][3] In mammalian cell, it has a function in the regulation of the cell cycle, chromatin modification, activation and inhibition of transcription initiation, control of transcription elongation, RNA export, nuclear RNA surveillance, and DNA damage repair in nucleus. Ccr4–Not complex plays an important role in mRNA decay and protein quality control in the cytoplasm.[9]

Subunits

The human CCR4-Not complex is composed of structural (non-catalytic) subunits and those that have exonuclease and E3 ligase activity. Some but not all of the human subunits are conserved in budding yeast.[10] In yeast the complex has nine core subunits, comprising Ccr4 (carbon catabolite repression), Caf proteins (Ccr4 associated factor) (Caf1, Caf40, Caf130) and Not proteins (Not1, Not2, Not3, Not4, and Not5).[11]

Subunit MW (kDa)[A] Key Features
CNOT1 267 "Scaffold" with non-catalytic function. Linked to the maintenance of embryonic stem cells.[12]
CNOT2 60 Structural component. Linked to the maintenance of embryonic stem cells.[12]
CNOT3 82 Structural component. Linked to the maintenance of embryonic stem cells.[13][12]
CNOT4 64 Active as E3 ubiquitin ligase.[7]
CNOT6 63 3′-5′ exonuclease with preference for polyadenylated mRNA substates.[5] Has a human paralog CNOT6L.
CNOT7 33 3′-5′ exonuclease that is partially redundant with CNOT8.[4]
CNOT8 34 3′-5′ exonuclease.[4]
CNOT9 34 Serves a non-catalytic function.[14]
CNOT10 82 Non-catalytic subunit that forms a module with CNOT11 that is absent in fungi.[15]
CNOT11 55 Non-catalytic subunit that forms a module with CNOT10 that is absent in fungi.[15]

A Molecular weight of human subunits from Uniprot.

See also

References

  1. ↑ Boland, Andreas; Chen, Ying; Raisch, Tobias; Jonas, Stefanie; Kuzuoğlu-Öztürk, Duygu; Wohlbold, Lara; Weichenrieder, Oliver; Izaurralde, Elisa (2013-10-13). "Structure and assembly of the NOT module of the human CCR4–NOT complex". Nature Structural & Molecular Biology (Springer Science and Business Media LLC) 20 (11): 1289–1297. doi:10.1038/nsmb.2681. ISSN 1545-9993. PMID 24121232. 
  2. ↑ 2.0 2.1 Collart, Martine A. (2016-01-29). "The Ccr4-Not complex is a key regulator of eukaryotic gene expression". Wiley Interdisciplinary Reviews: RNA (Wiley) 7 (4): 438–454. doi:10.1002/wrna.1332. ISSN 1757-7004. PMID 26821858. 
  3. ↑ 3.0 3.1 Miller, Jason E.; Reese, Joseph C. (2012-03-15). "Ccr4-Not complex: the control freak of eukaryotic cells". Critical Reviews in Biochemistry and Molecular Biology (Informa UK Limited) 47 (4): 315–333. doi:10.3109/10409238.2012.667214. ISSN 1040-9238. PMID 22416820. 
  4. ↑ 4.0 4.1 4.2 Aslam, Akhmed; Mittal, Saloni; Koch, Frederic; Andrau, Jean-Christophe; Winkler, G. Sebastiaan (2009). Wickens, Marvin. ed. "The Ccr4–Not Deadenylase Subunits CNOT7 and CNOT8 Have Overlapping Roles and Modulate Cell Proliferation". Molecular Biology of the Cell (American Society for Cell Biology (ASCB)) 20 (17): 3840–3850. doi:10.1091/mbc.e09-02-0146. ISSN 1059-1524. PMID 19605561. 
  5. ↑ 5.0 5.1 "CCR4, a 3′-5′ poly(A) RNA and ssDNA exonuclease, is the catalytic component of the cytoplasmic deadenylase". EMBO J 21 (6): 1414–26. Mar 2002. doi:10.1093/emboj/21.6.1414. PMID 11889047. 
  6. ↑ "Entrez Gene: CNOT6 CCR4-NOT transcription complex, subunit 6". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57472. 
  7. ↑ 7.0 7.1 Albert, Thomas K.; Hanzawa, Hiroyuki; Legtenberg, Yvonne I.A.; de Ruwe, Marjolein J.; van den Heuvel, Fiona A.J.; Collart, Martine A.; Boelens, Rolf; Timmers, H.Th.Marc (2002-02-01). "Identification of a ubiquitin-protein ligase subunit within the CCR4-NOT transcription repressor complex". The EMBO Journal (Wiley) 21 (3): 355–364. doi:10.1093/emboj/21.3.355. ISSN 0261-4189. PMID 11823428. 
  8. ↑ Stowell, James A. W.; Webster, Michael W.; Kögel, Alexander; Wolf, Jana; Shelley, Kathryn L.; Passmore, Lori A. (2016-11-15). "Reconstitution of Targeted Deadenylation by the Ccr4-Not Complex and the YTH Domain Protein Mmi1". Cell Reports 17 (8): 1978–1989. doi:10.1016/j.celrep.2016.10.066. ISSN 2211-1247. PMID 27851962. PMC 5120349. https://pubmed.ncbi.nlm.nih.gov/27851962/. 
  9. ↑ Chalabi Hagkarim, Nafiseh; Grand, Roger J. (2020-10-29). "The Regulatory Properties of the Ccr4–Not Complex". Cells 9 (11): 2379. doi:10.3390/cells9112379. ISSN 2073-4409. PMID 33138308. 
  10. ↑ Albert, T. K. (2000-02-01). "Isolation and characterization of human orthologs of yeast CCR4-NOT complex subunits". Nucleic Acids Research (Oxford University Press (OUP)) 28 (3): 809–817. doi:10.1093/nar/28.3.809. ISSN 1362-4962. PMID 10637334. 
  11. ↑ Collart, Martine A (2003-08-14). "Global control of gene expression in yeast by the Ccr4-Not complex". Gene 313: 1–16. doi:10.1016/S0378-1119(03)00672-3. ISSN 0378-1119. https://www.sciencedirect.com/science/article/pii/S0378111903006723. 
  12. ↑ 12.0 12.1 12.2 Zheng, Xiaofeng; Dumitru, Raluca; Lackford, Brad L.; Freudenberg, Johannes M.; Singh, Ajeet P.; Archer, Trevor K.; Jothi, Raja; Hu, Guang (2012-04-09). "Cnot1, Cnot2, and Cnot3 Maintain Mouse and Human ESC Identity and Inhibit Extraembryonic Differentiation". Stem Cells (Wiley) 30 (5): 910–922. doi:10.1002/stem.1070. ISSN 1066-5099. PMID 22367759. 
  13. ↑ Hu, G.; Kim, J.; Xu, Q.; Leng, Y.; Orkin, S. H.; Elledge, S. J. (2009-04-01). "A genome-wide RNAi screen identifies a new transcriptional module required for self-renewal". Genes & Development (Cold Spring Harbor Laboratory) 23 (7): 837–848. doi:10.1101/gad.1769609. ISSN 0890-9369. PMID 19339689. 
  14. ↑ Pavanello, Lorenzo; Hall, Benjamin; Airhihen, Blessing; Winkler, Gerlof Sebastiaan (2018-11-09). central region of CNOT1 and CNOT9 stimulate deadenylation by the Ccr4-Not nuclease module "The central region of CNOT1 and CNOT9 stimulates deadenylation by the Ccr4–Not nuclease module". Biochemical Journal (Portland Press Ltd.) 475 (21): 3437–3450. doi:10.1042/bcj20180456. ISSN 0264-6021. PMID 30309886. https://nottingham-repository.worktribe.com/1162954/1/The central region of CNOT1 and CNOT9 stimulate deadenylation by the Ccr4-Not nuclease module. 
  15. ↑ 15.0 15.1 Mauxion, Fabienne; Prève, Brigitte; Séraphin, Bertrand (2013). "C2ORF29/CNOT11 and CNOT10 form a new module of the CCR4-NOT complex". RNA Biology (Informa UK Limited) 10 (2): 267–276. doi:10.4161/rna.23065. ISSN 1547-6286. PMID 23232451. 



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