CCR4-Not

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Structure of human CNOT1-CNOT2-CNOT3 module (PDB 4C0D). PDB-4C0D-CNOT1-2-3-TC.png
Structure of human CNOT1-CNOT2-CNOT3 module (PDB 4C0D).

Carbon Catabolite Repression 4—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]

Contents

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]

SubunitMW (kDa) [A] Key Features
CNOT1 267"Scaffold" with non-catalytic function. Linked to the maintenance of embryonic stem cells. [12]
CNOT2 60Structural component. Linked to the maintenance of embryonic stem cells. [12]
CNOT3 82Structural component. Linked to the maintenance of embryonic stem cells. [13] [12]
CNOT4 64Active as E3 ubiquitin ligase. [7]
CNOT6 633′-5′ exonuclease with preference for polyadenylated mRNA substates. [5] Has a human paralog CNOT6L.
CNOT7 333′-5′ exonuclease that is partially redundant with CNOT8. [4]
CNOT8 343′-5′ exonuclease. [4]
CNOT9 34Serves a non-catalytic function. [14]
CNOT10 82Non-catalytic subunit that forms a module with CNOT11 that is absent in fungi. [15]
CNOT11 55Non-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. 20 (11). Springer Science and Business Media LLC: 1289–1297. doi:10.1038/nsmb.2681. ISSN   1545-9993. PMID   24121232. S2CID   24288483.
  2. 1 2 Collart, Martine A. (2016-01-29). "The Ccr4-Not complex is a key regulator of eukaryotic gene expression". Wiley Interdisciplinary Reviews: RNA. 7 (4). Wiley: 438–454. doi:10.1002/wrna.1332. ISSN   1757-7004. PMC   5066686 . PMID   26821858.
  3. 1 2 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. 47 (4). Informa UK Limited: 315–333. doi:10.3109/10409238.2012.667214. ISSN   1040-9238. PMC   3376659 . PMID   22416820.
  4. 1 2 3 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. 20 (17). American Society for Cell Biology (ASCB): 3840–3850. doi:10.1091/mbc.e09-02-0146. ISSN   1059-1524. PMC   2735483 . PMID   19605561.
  5. 1 2 Chen J, Chiang YC, Denis CL (Mar 2002). "CCR4, a 3′-5′ poly(A) RNA and ssDNA exonuclease, is the catalytic component of the cytoplasmic deadenylase". EMBO J. 21 (6): 1414–26. doi:10.1093/emboj/21.6.1414. PMC   125924 . PMID   11889047.
  6. ↑ "Entrez Gene: CNOT6 CCR4-NOT transcription complex, subunit 6".
  7. 1 2 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. 21 (3). Wiley: 355–364. doi:10.1093/emboj/21.3.355. ISSN   0261-4189. PMC   125831 . 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. PMC   5120349 . PMID   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. PMC   7692201 . PMID   33138308.
  10. ↑ Albert, T. K. (2000-02-01). "Isolation and characterization of human orthologs of yeast CCR4-NOT complex subunits". Nucleic Acids Research. 28 (3). Oxford University Press (OUP): 809–817. doi: 10.1093/nar/28.3.809 . ISSN   1362-4962. PMC   102560 . 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. PMID   12957374.
  12. 1 2 3 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. 30 (5). Wiley: 910–922. doi:10.1002/stem.1070. ISSN   1066-5099. PMC   3787717 . 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. 23 (7). Cold Spring Harbor Laboratory: 837–848. doi: 10.1101/gad.1769609 . ISSN   0890-9369. PMC   2666338 . PMID   19339689.
  14. ↑ Pavanello, Lorenzo; Hall, Benjamin; Airhihen, Blessing; Winkler, Gerlof Sebastiaan (2018-11-09). "The central region of CNOT1 and CNOT9 stimulates deadenylation by the Ccr4–Not nuclease module". Biochemical Journal. 475 (21). Portland Press Ltd.: 3437–3450. doi:10.1042/bcj20180456. ISSN   0264-6021. PMID   30309886. S2CID   52962278.
  15. 1 2 Mauxion, Fabienne; Prève, Brigitte; Séraphin, Bertrand (2013). "C2ORF29/CNOT11 and CNOT10 form a new module of the CCR4-NOT complex". RNA Biology. 10 (2). Informa UK Limited: 267–276. doi: 10.4161/rna.23065 . ISSN   1547-6286. PMC   3594285 . PMID   23232451.
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