CCR4-Not

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 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]

Structure of human CNOT1-CNOT2-CNOT3 module (PDB 4C0D).[1]

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.[8]

Subunit	MW (kDa)^[A]	Key Features
CNOT1	267	"Scaffold" with non-catalytic function. Linked to the maintenance of embryonic stem cells.[9]
CNOT2	60	Structural component. Linked to the maintenance of embryonic stem cells.[9]
CNOT3	82	Structural component. Linked to the maintenance of embryonic stem cells.[10][9]
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 CNOT7.[4]
CNOT8	34	3′-5′ exonuclease.[4]
CNOT9	34	Serves a non-catalytic function.[11]
CNOT10	82	Non-catalytic subunit that forms a module with CNOT11 that is absent in fungi.[12]
CNOT11	55	Non-catalytic subunit that forms a module with CNOT10 that is absent in fungi.[12]

^A Molecular weight of human subunits from Uniprot.

See also

• Deadenylation
• Gene expression

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. 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. PMC 5066686. PMID 26821858.
3. 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. PMC 3376659. PMID 22416820.
4. 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. PMC 2735483. PMID 19605561.
5. 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. 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. PMC 125831. PMID 11823428.
8. 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. PMC 102560. PMID 10637334.
9. 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. PMC 3787717. PMID 22367759.
10. 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. PMC 2666338. PMID 19339689.
11. 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. Portland Press Ltd. 475 (21): 3437–3450. doi:10.1042/bcj20180456. ISSN 0264-6021. PMID 30309886.
12. 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.