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The Ccr4-Not Complex: Architecture and Structural Insights

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Book cover Macromolecular Protein Complexes

Part of the book series: Subcellular Biochemistry ((SCBI,volume 83))

Abstract

The Ccr4-Not complex is an essential multi-subunit protein complex that plays a fundamental role in eukaryotic mRNA metabolism and has a multitude of different roles that impact eukaryotic gene expression . It has a conserved core of three Not proteins, the Ccr4 protein, and two Ccr4 associated factors, Caf1 and Caf40. A fourth Not protein, Not4, is conserved, but is only a stable subunit of the complex in yeast. Certain subunits have been duplicated during evolution, with functional divergence, such as Not3 in yeast, and Ccr4 or Caf1 in human. However the complex includes only one homolog for each protein. In addition, species-specific subunits are part of the complex, such as Caf130 in yeast or Not10 and Not11 in human. Two conserved catalytic functions are associated with the complex, deadenylation and ubiquitination . The complex adopts an L-shaped structure, in which different modules are bound to a large Not1 scaffold protein. In this chapter we will summarize our current knowledge of the architecture of the complex and of the structure of its constituents.

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References

  • Ajiro M, Katagiri T, Ueda K, Nakagawa H, Fukukawa C, Lin ML, Park JH, Nishidate T, Daigo Y, Nakamura Y (2009) Involvement of RQCD1 overexpression, a novel cancer-testis antigen, in the Akt pathway in breast cancer cells. Int J Oncol 35(4):673–681

    CAS  PubMed  Google Scholar 

  • Albert TK, Hanzawa H, Legtenberg YI, de Ruwe MJ, van den Heuvel FA, Collart MA, Boelens R, Timmers HT (2002) Identification of a ubiquitin-protein ligase subunit within the CCR4-NOT transcription repressor complex. Embo J 21(3):355–364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alhusaini N, Coller J (2016) The deadenylase components Not2p, Not3p, and Not5p promote mRNA decapping. RNA 22(5):709–721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andersen KR, Jonstrup AT, Van LB, Brodersen DE (2009) The activity and selectivity of fission yeast Pop2p are affected by a high affinity for Zn2+ and Mn2+ in the active site. RNA 15(5):850–861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aslam A, Mittal S, Koch F, Andrau JC, Winkler GS (2009) The Ccr4-NOT deadenylase subunits CNOT7 and CNOT8 have overlapping roles and modulate cell proliferation. Mol Biol Cell 20(17):3840–3850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Azzouz N, Panasenko OO, Colau G, Collart MA (2009) The CCR4-NOT complex physically and functionally interacts with TRAMP and the nuclear exosome. PLoS One 4(8):e6760

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bartlam M, Yamamoto T (2010) The structural basis for deadenylation by the CCR4-NOT complex. Protein Cell 1(5):443–452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Basquin J, Roudko VV, Rode M, Basquin C, Seraphin B, Conti E (2012) Architecture of the nuclease module of the yeast Ccr4-not complex: the Not1-Caf1-Ccr4 interaction. Mol Cell 48(2):207–218

    Article  CAS  PubMed  Google Scholar 

  • Bawankar P, Loh B, Wohlbold L, Schmidt S, Izaurralde E (2013) NOT10 and C2orf29/NOT11 form a conserved module of the CCR4-NOT complex that docks onto the NOT1 N-terminal domain. RNA Biol 10(2):228–244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berthet C, Morera AM, Asensio MJ, Chauvin MA, Morel AP, Dijoud F, Magaud JP, Durand P, Rouault JP (2004) CCR4-associated factor CAF1 is an essential factor for spermatogenesis. Mol Cell Biol 24(13):5808–5820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bhandari D, Raisch T, Weichenrieder O, Jonas S, Izaurralde E (2014) Structural basis for the Nanos-mediated recruitment of the CCR4-NOT complex and translational repression. Genes Dev 28(8):888–901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bhaskar V, Roudko V, Basquin J, Sharma K, Urlaub H, Seraphin B, Conti E (2013) Structure and RNA-binding properties of the Not1-Not2-Not5 module of the yeast Ccr4-Not complex. Nat Struct Mol Biol 20(11):1281–1288

    Article  CAS  PubMed  Google Scholar 

  • Bhaskar V, Basquin J, Conti E (2015) Architecture of the ubiquitylation module of the yeast Ccr4-Not complex. Structure 23(5):921–928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boland A, Chen Y, Raisch T, Jonas S, Kuzuoglu-Ozturk D, Wohlbold L, Weichenrieder O, Izaurralde E (2013) Structure and assembly of the NOT module of the human CCR4-NOT complex. Nat Struct Mol Biol 20(11):1289–1297

    Article  CAS  PubMed  Google Scholar 

  • Chapat C, Corbo L (2014) Novel roles of the CCR4-NOT complex. Wiley Interdiscip Rev RNA 5(6):883–901

    Article  CAS  PubMed  Google Scholar 

  • Chapat C, Kolytcheff C, Le Romancer M, Auboeuf D, De La Grange P, Chettab K, Sentis S, Corbo L (2013) hCAF1/CNOT7 regulates interferon signalling by targeting STAT1. EMBO J 32(5):688–700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen J, Rappsilber J, Chiang YC, Russell P, Mann M, Denis CL (2001) Purification and characterization of the 1.0 MDa CCR4-NOT complex identifies two novel components of the complex. J Mol Biol 314(4):683–694

    Article  CAS  PubMed  Google Scholar 

  • Chen C, Ito K, Takahashi A, Wang G, Suzuki T, Nakazawa T, Yamamoto T, Yokoyama K (2011) Distinct expression patterns of the subunits of the CCR4-NOT deadenylase complex during neural development. Biochem Biophys Res Commun 411(2):360–364

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Boland A, Kuzuoglu-Ozturk D, Bawankar P, Loh B, Chang CT, Weichenrieder O, Izaurralde E (2014) A DDX6-CNOT1 complex and W-binding pockets in CNOT9 reveal direct links between miRNA target recognition and silencing. Mol Cell 54(5):737–750

    Article  CAS  PubMed  Google Scholar 

  • Chicoine J, Benoit P, Gamberi C, Paliouras M, Simonelig M, Lasko P (2007) Bicaudal-C recruits CCR4-NOT deadenylase to target mRNAs and regulates oogenesis, cytoskeletal organization, and its own expression. Developmental Cell 13(5):691–704

    Article  CAS  PubMed  Google Scholar 

  • Collart MA (2003) Global control of gene expression in yeast by the Ccr4-Not complex. Gene 313:1–16

    Article  CAS  PubMed  Google Scholar 

  • Collart MA (2013) The NOT4 RING E3 ligase: a relevant player in co-translational quality control. ISRN Mol Biol 2013:1–19

    Article  CAS  Google Scholar 

  • Collart MA (2016) The Ccr4-Not complex is a key regulator of eukaryotic gene expression. Wiley Interdiscip Rev RNA 7(4):438–454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Collart MA, Panasenko OO (2012) The Ccr4--not complex. Gene 492(1):42–53

    Article  CAS  PubMed  Google Scholar 

  • Collart M, Panasenko O, Nikolaev S (2012) The Not3/5 subunit of the Ccr4-Not complex: a central regulator of gene expression that integrates signals between the cytoplasm and the nucleus in eukaryotic cells. Cell Signal 25(4):743–751

    Article  PubMed  CAS  Google Scholar 

  • Cook WJ, Jeffrey LC, Xu Y, Chau V (1993) Tertiary structures of class I ubiquitin-conjugating enzymes are highly conserved: crystal structure of yeast Ubc4. Biochemistry 32(50):13809–13817

    Article  CAS  PubMed  Google Scholar 

  • Cooper KF, Scarnati MS, Krasley E, Mallory MJ, Jin C, Law MJ, Strich R (2012) Oxidative-stress-induced nuclear to cytoplasmic relocalization is required for Not4-dependent cyclin C destruction. J Cell Sci 125(Pt 4):1015–1026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Keersmaecker K, Atak ZK, Li N, Vicente C, Patchett S, Girardi T, Gianfelici V, Geerdens E, Clappier E, Porcu M, Lahortiga I, Luca R, Yan J, Hulselmans G, Vranckx H, Vandepoel R, Sweron B, Jacobs K, Mentens N, Wlodarska I, Cauwelier B, Cloos J, Soulier J, Uyttebroeck A, Bagni C, Hassan BA, Vandenberghe P, Johnson AW, Aerts S, Cools J (2013) Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia. Nat Genet 45(2):186–190

    Article  CAS  PubMed  Google Scholar 

  • Dimitrova LN, Kuroha K, Tatematsu T, Inada T (2009) Nascent peptide-dependent translation arrest leads to Not4p-mediated protein degradation by the proteasome. J Biol Chem 284(16):10343–10352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doidge R, Mittal S, Aslam A, Winkler GS (2012) Deadenylation of cytoplasmic mRNA by the mammalian Ccr4-Not complex. Biochem Soc Trans 40(4):896–901

    Article  CAS  PubMed  Google Scholar 

  • Draper MP, Salvadore C, Denis CL (1995) Identification of a mouse protein whose homolog in Saccharomyces cerevisiae is a component of the CCR4 transcriptional regulatory complex. Mol. Cell. Biol. 15(7):3487–3495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fabian MR, Frank F, Rouya C, Siddiqui N, Lai WS, Karetnikov A, Blackshear PJ, Nagar B, Sonenberg N (2013) Structural basis for the recruitment of the human CCR4-NOT deadenylase complex by tristetraprolin. Nat Struct Mol Biol 20(6):735–739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Faraji F, Hu Y, Wu G, Goldberger NE, Walker RC, Zhang J, Hunter KW (2014) An integrated systems genetics screen reveals the transcriptional structure of inherited predisposition to metastatic disease. Genome Res 24(2):227–240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garapaty S, Mahajan MA, Samuels HH (2008) Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1. J Biol Chem 283(11):6806–6816

    Article  CAS  PubMed  Google Scholar 

  • Garces RG, Gillon W, Pai EF (2007) Atomic model of human Rcd-1 reveals an armadillo-like-repeat protein with in vitro nucleic acid binding properties. Protein Sci 16(2):176–188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldstrohm AC, Wickens M (2008) Multifunctional deadenylase complexes diversify mRNA control. Nat Rev Mol Cell Biol 9(4):337–344

    Article  CAS  PubMed  Google Scholar 

  • Goldstrohm AC, Hook BA, Seay DJ, Wickens M (2006) PUF proteins bind Pop2p to regulate messenger RNAs. Nat Struct Mol Biol 13(6):533–539

    Article  CAS  PubMed  Google Scholar 

  • Gronholm J, Kaustio M, Myllymaki H, Kallio J, Saarikettu J, Kronhamn J, Valanne S, Silvennoinen O, Ramet M (2012) Not4 enhances JAK/STAT pathway-dependent gene expression in Drosophila and in human cells. FASEB J 26(3):1239–1250

    Article  CAS  PubMed  Google Scholar 

  • Gulshan K, Thommandru B, Moye-Rowley WS (2012) Proteolytic degradation of the Yap1 transcription factor is regulated by subcellular localization and the E3 ubiquitin ligase Not4. J Biol Chem 287(32):26796–26805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gutierrez-Camino A, Lopez-Lopez E, Martin-Guerrero I, Pinan MA, Garcia-Miguel P, Sanchez-Toledo J, Carbone Baneres A, Uriz J, Navajas A, Garcia-Orad A (2014) Noncoding RNA-related polymorphisms in pediatric acute lymphoblastic leukemia susceptibility. Pediatr Res 75(6):767–773

    Article  CAS  PubMed  Google Scholar 

  • Haas M, Siegert M, Schürmann A, Sodeik B, Wolfes H (2004) c-Myb protein interacts with Rcd-1, a component of the CCR4 transcription mediator complex. Biochem. 43:8152–8159

    Article  CAS  Google Scholar 

  • Halter D, Collart MA, Panasenko OO (2014) The Not4 E3 ligase and CCR4 deadenylase play distinct roles in protein quality control. PLoS One 9(1):e86218

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hanzawa H, de Ruwe MJ, Albert TK, van Der Vliet PC, Timmers HT, Boelens R (2001) The structure of the C4C4 ring finger of human NOT4 reveals features distinct from those of C3HC4 RING fingers. J Biol Chem 276(13):10185–10190

    Article  CAS  PubMed  Google Scholar 

  • Haworth J, Alver RC, Anderson M, Bielinsky AK (2010) Ubc4 and Not4 regulate steady-state levels of DNA polymerase-alpha to promote efficient and accurate DNA replication. Mol Biol Cell 21(18):3205–3219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hiroi N, Ito T, Yamamoto H, Ochiya T, Jinno S, Okayama H (2002) Mammalian Rcd1 is a novel transcriptional cofactor that mediates retinoic acid-induced cell differentiation. EMBO J. 21:5235–5244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Horiuchi M, Takeuchi K, Noda N, Muroya N, Suzuki T, Nakamura T, Kawamura-Tsuzuku J, Takahasi K, Yamamoto T, Inagaki F (2009) Structural basis for the antiproliferative activity of the Tob-hCaf1 complex. J Biol Chem 284(19):13244–13255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inada T, Makino S (2014) Novel roles of the multi-functional CCR4-NOT complex in post-transcriptional regulation. Front Genet 5:135

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Inoue T, Morita M, Hijikata A, Fukuda-Yuzawa Y, Adachi S, Isono K, Ikawa T, Kawamoto H, Koseki H, Natsume T, Fukao T, Ohara O, Yamamoto T, Kurosaki T (2015) CNOT3 contributes to early B cell development by controlling Igh rearrangement and p53 mRNA stability. J Exp Med 212(9):1465–1479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamath RS, Ahringer J (2003) Genome-wide RNAi screening in Caenorhabditis elegans. Methods 30:313–321

    Article  CAS  PubMed  Google Scholar 

  • Krueger KE, Ghosh AK, Krom BP, Cihlar RL (2004) Deletion of the NOT4 gene impairs hyphal development and pathogenicity in Candida albicans. Microbiology 150(Pt 1):229–240

    Article  CAS  PubMed  Google Scholar 

  • Lau NC, Kolkman A, van Schaik FM, Mulder KW, Pijnappel WW, Heck AJ, Timmers HT (2009) Human Ccr4-Not complexes contain variable deadenylase subunits. Biochem J 422(3):443–453

    Article  CAS  PubMed  Google Scholar 

  • Liu HY, Chiang YC, Pan J, Chen J, Salvadore C, Audino DC, Badarinarayana V, Palaniswamy V, Anderson B, Denis CL (2001) Characterization of CAF4 and CAF16 reveals a functional connection between the CCR4-NOT complex and a subset of SRB proteins of the RNA polymerase II holoenzyme. J Biol Chem 276(10):7541–7548

    Article  CAS  PubMed  Google Scholar 

  • Maeda I, Kohara Y, Yamamoto M, Sugimoto A (2001) Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi. Current Biol. 11:171–176

    Article  CAS  Google Scholar 

  • Maillet L, Tu C, Hong YK, Shuster EO, Collart MA (2000) The essential function of Not1 lies within the Ccr4-Not complex. J Mol Biol 303(2):131–143

    Article  CAS  PubMed  Google Scholar 

  • Malvar T, Biron RW, Kaback DB, Denis CL (1992) The CCR4 protein from Saccharomyces cerevisiae contains a leucine-rich repeat region which is required for its control of ADH2 gene expression. Genetics 132(4):951–962

    CAS  PubMed  PubMed Central  Google Scholar 

  • Maragozidis P, Karangeli M, Labrou M, Dimoulou G, Papaspyrou K, Salataj E, Pournaras S, Matsouka P, Gourgoulianis KI, Balatsos NA (2012) Alterations of deadenylase expression in acute leukemias: evidence for poly(a)-specific ribonuclease as a potential biomarker. Acta Haematol 128(1):39–46

    Article  CAS  PubMed  Google Scholar 

  • Mathys H, Basquin J, Ozgur S, Czarnocki-Cieciura M, Bonneau F, Aartse A, Dziembowski A, Nowotny M, Conti E, Filipowicz W (2014) Structural and biochemical insights to the role of the CCR4-NOT complex and DDX6 ATPase in microRNA repression. Mol Cell 54(5):751–765

    Article  CAS  PubMed  Google Scholar 

  • Mauxion F, Preve B, Seraphin B (2013) C2ORF29/CNOT11 and CNOT10 form a new module of the CCR4-NOT complex. RNA Biol 10(2):267–276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mazzoni C, Serafini A, Falcone C (2005) The inactivation of KlNOT4, a Kluyveromyces lactis gene encoding a component of the CCR4-NOT complex, reveals new regulatory functions. Genetics 170(3):1023–1032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mersman DP, Du HN, Fingerman IM, South PF, Briggs SD (2009) Polyubiquitination of the demethylase Jhd2 controls histone methylation and gene expression. Genes Dev 23(8):951–962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller JE, Reese JC (2012) Ccr4-Not complex: the control freak of eukaryotic cells. Critical reviews in biochemistry and molecular biology 47(4):315–333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mittal S, Aslam A, Doidge R, Medica R, Winkler GS (2011) The Ccr4a (CNOT6) and Ccr4b (CNOT6L) deadenylase subunits of the human Ccr4-Not complex contribute to the prevention of cell death and senescence. Molecular biology of the cell 22(6):748–758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morita M, Suzuki T, Nakamura T, Yokoyama K, Miyasaka T, Yamamoto T (2007) Depletion of mammalian CCR4b deadenylase triggers elevation of the p27Kip1 mRNA level and impairs cell growth. Mol Cell Biol 27(13):4980–4990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morita M, Oike Y, Nagashima T, Kadomatsu T, Tabata M, Suzuki T, Nakamura T, Yoshida N, Okada M, Yamamoto T (2011) Obesity resistance and increased hepatic expression of catabolism-related mRNAs in Cnot3+/− mice. EMBO J 30(22):4678–4691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muhlrad D, Parker R (2005) The yeast EDC1 mRNA undergoes deadenylation-independent decapping stimulated by Not2p, Not4p, and Not5p. Embo J 24(5):1033–1045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mulder KW, Winkler GS, Timmers HT (2005) DNA damage and replication stress induced transcription of RNR genes is dependent on the Ccr4-Not complex. Nucleic Acids Res 33(19):6384–6392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mulder KW, Brenkman AB, Inagaki A, van den Broek NJ, Timmers HT (2007) Regulation of histone H3K4 tri-methylation and PAF complex recruitment by the Ccr4-Not complex. Nucleic Acids Res 35(7):2428–2439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakamura T, Yao R, Ogawa T, Suzuki T, Ito C, Tsunekawa N, Inoue K, Ajima R, Miyasaka T, Yoshida Y, Ogura A, Toshimori K, Noce T, Yamamoto T, Noda T (2004) Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta. Nat Genet 36(5):528–533

    Article  CAS  PubMed  Google Scholar 

  • Nasertorabi F, Batisse C, Diepholz M, Suck D, Bottcher B (2011) Insights into the structure of the CCR4-NOT complex by electron microscopy. FEBS Letters 585:2182–2186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neely GG, Kuba K, Cammarato A, Isobe K, Amann S, Zhang L, Murata M, Elmen L, Gupta V, Arora S, Sarangi R, Dan D, Fujisawa S, Usami T, Xia CP, Keene AC, Alayari NN, Yamakawa H, Elling U, Berger C, Novatchkova M, Koglgruber R, Fukuda K, Nishina H, Isobe M, Pospisilik JA, Imai Y, Pfeufer A, Hicks AA, Pramstaller PP, Subramaniam S, Kimura A, Ocorr K, Bodmer R, Penninger JM (2010) A global in vivo Drosophila RNAi screen identifies NOT3 as a conserved regulator of heart function. Cell 141(1):142–153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nousch M, Techritz N, Hampel D, Millonigg S, Eckmann CR (2013) The Ccr4-Not deadenylase complex constitutes the main poly(A) removal activity in C. elegans. J Cell Sci 126(Pt 18):4274–4285

    Article  CAS  PubMed  Google Scholar 

  • Okazaki N, Okazaki K, Watanabe Y, Kato-Hayashhi M, Yamamoto M, Okayama H (1998) Novel factor highly conserved among eukaryotes controls sexual development in fission yeast. Mol. Cell. Biol. 18:887–895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ozgur S, Basquin J, Kamenska A, Filipowicz W, Standart N, Conti E (2015) Structure of a Human 4E-T/DDX6/CNOT1 Complex Reveals the Different Interplay of DDX6-Binding Proteins with the CCR4-NOT Complex. Cell Rep 13(4):703–711

    Article  CAS  PubMed  Google Scholar 

  • Panasenko OO (2014) The role of the E3 ligase Not4 in cotranslational quality control. Front Genet 5:141

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Panasenko OO, Collart MA (2012) Presence of Not5 and ubiquitinated Rps7A in polysome fractions depends upon the Not4 E3 ligase. Molecular microbiology 83(3):640–653

    Article  CAS  PubMed  Google Scholar 

  • Panasenko O, Landrieux E, Feuermann M, Finka A, Paquet N, Collart MA (2006) The yeast Ccr4-Not complex controls ubiquitination of the nascent-associated polypeptide (NAC-EGD) complex. J Biol Chem 281(42):31389–31398

    Article  CAS  PubMed  Google Scholar 

  • Panepinto JC, Heinz E, Traven A (2013) The cellular roles of Ccr4-NOT in model and pathogenic fungi-implications for fungal virulence. Front Genet 4:302

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Petit AP, Wohlbold L, Bawankar P, Huntzinger E, Schmidt S, Izaurralde E, Weichenrieder O (2012) The structural basis for the interaction between the CAF1 nuclease and the NOT1 scaffold of the human CCR4-NOT deadenylase complex. Nucleic Acids Res 40(21):11058–11072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Preissler S, Reuther J, Koch M, Scior A, Bruderek M, Frickey T, Deuerling E (2015) Not4-dependent translational repression is important for cellular protein homeostasis in yeast. EMBO J 34(14):1905–1924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reese JC (2013) The control of elongation by the yeast Ccr4-not complex. Biochim Biophys Acta 1829(1):127–133

    Article  CAS  PubMed  Google Scholar 

  • Sandler H, Kreth J, Timmers HT, Stoecklin G (2011) Not1 mediates recruitment of the deadenylase Caf1 to mRNAs targeted for degradation by tristetraprolin. Nucleic acids research 39(10):4373–4386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwede A, Ellis L, Luther J, Carrington M, Stoecklin G, Clayton C (2008) A role for Caf1 in mRNA deadenylation and decay in trypanosomes and human cells. Nucleic Acids Res 36(10):3374–3388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seiden-Long IM, Brown KR, Shih W, Wigle DA, Radulovich N, Jurisica I, Tsao MS (2006) Transcriptional targets of hepatocyte growth factor signaling and Ki-ras oncogene activation in colorectal cancer. Oncogene 25(1):91–102

    CAS  PubMed  Google Scholar 

  • Shirai YT, Suzuki T, Morita M, Takahashi A, Yamamoto T (2014) Multifunctional roles of the mammalian CCR4-NOT complex in physiological phenomena. Front Genet 5:286

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sun HY, Kim N, Hwang CS, Yoo JY (2015) Protein Degradation of RNA Polymerase II-Association Factor 1(PAF1) Is Controlled by CNOT4 and 26S Proteasome. PLoS One 10(5):e0125599

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Suzuki A, Igarashi K, Aisaki K, Kanno J, Saga Y (2010) NANOS2 interacts with the CCR4-NOT deadenylation complex and leads to suppression of specific RNAs. Proceedings of the National Academy of Sciences of the United States of America 107(8):3594–3599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki T, Kikuguchi C, Sharma S, Sasaki T, Tokumasu M, Adachi S, Natsume T, Kanegae Y, Yamamoto T (2015) CNOT3 suppression promotes necroptosis by stabilizing mRNAs for cell death-inducing proteins. Sci Rep 5:14779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tay Y, Kats L, Salmena L, Weiss D, Tan SM, Ala U, Karreth F, Poliseno L, Provero P, Di Cunto F, Lieberman J, Rigoutsos I, Pandolfi PP (2011) Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell 147(2):344–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Temme C, Zaessinger S, Meyer S, Simonelig M, Wahle E (2004) A complex containing the CCR4 and CAF1 proteins is involved in mRNA deadenylation in Drosophila. Embo J 23(14):2862–2871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Temme C, Zhang L, Kremmer E, Ihling C, Chartier A, Sinz A, Simonelig M, Wahle E (2010) Subunits of the Drosophila CCR4-NOT complex and their roles in mRNA deadenylation. RNA 16(7):1356–1370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Temme C, Simonelig M, Wahle E (2014) Deadenylation of mRNA by the CCR4-NOT complex in Drosophila: molecular and developmental aspects. Front Genet 5:143

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Thore S, Mauxion F, Seraphin B, Suck D (2003) X-ray structure and activity of the yeast Pop2 protein: a nuclease subunit of the mRNA deadenylase complex. EMBO Rep 4(12):1150–1155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tucker M, Staples RR, Valencia-Sanchez MA, Muhlrad D, Parker R (2002) Ccr4p is the catalytic subunit of a Ccr4p/Pop2p/Notp mRNA deadenylase complex in Saccharomyces cerevisiae. EMBO J. 21:1427–1436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ukleja M, Cuellar J, Siwaszek A, Kasprzak JM, Czarnocki-Cieciura M, Bujnicki JM, Dziembowski A, Valpuesta JM (2016) The architecture of the Schizosaccharomyces pombe CCR4-NOT complex. Nat Commun 7:10433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Venturini G, Rose AM, Shah AZ, Bhattacharya SS, Rivolta C (2012) CNOT3 is a modifier of PRPF31 mutations in retinitis pigmentosa with incomplete penetrance. PLoS Genet 8(11):e1003040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Villanyi Z, Collart MA (2015) Ccr4-Not is at the core of the eukaryotic gene expression circuitry. Biochem Soc Trans 43(6):1253–1258

    Article  CAS  PubMed  Google Scholar 

  • Villanyi Z, Ribaud V, Kassem S, Panasenko OO, Pahi Z, Gupta I, Steinmetz L, Boros I, Collart MA (2014) The Not5 subunit of the ccr4-not complex connects transcription and translation. PLoS Genet 10(10):e1004569

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wahle E, Winkler GS (2013) RNA decay machines: deadenylation by the Ccr4-Not and Pan2-Pan3 complexes. Biochim Biophys Acta 1829(6–7):561–570

    Article  CAS  PubMed  Google Scholar 

  • Wang H, Morita M, Yang X, Suzuki T, Yang W, Wang J, Ito K, Wang Q, Zhao C, Bartlam M, Yamamoto T, Rao Z (2010) Crystal structure of the human CNOT6L nuclease domain reveals strict poly(A) substrate specificity. The EMBO journal 29(15):2566–2576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Washio-Oikawa K, Nakamura T, Usui M, Yoneda M, Ezura Y, Ishikawa I, Nakashima K, Noda T, Yamamoto T, Noda M (2007) Cnot7-null mice exhibit high bone mass phenotype and modulation of BMP actions. J Bone Miner Res 22(8):1217–1223

    Article  PubMed  Google Scholar 

  • Watanabe C, Morita M, Hayata T, Nakamoto T, Kikuguchi C, Li X, Kobayashi Y, Takahashi N, Notomi T, Moriyama K, Yamamoto T, Ezura Y, Noda M (2014) Stability of mRNA influences osteoporotic bone mass via CNOT3. Proc Natl Acad Sci U S A 111(7):2692–2697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong SQ, Behren A, Mar VJ, Woods K, Li J, Martin C, Sheppard KE, Wolfe R, Kelly J, Cebon J, Dobrovic A, McArthur GA (2015) Whole exome sequencing identifies a recurrent RQCD1 P131L mutation in cutaneous melanoma. Oncotarget 6(2):1115–1127

    Article  PubMed  Google Scholar 

  • Xu K, Bai Y, Zhang A, Zhang Q, Bartlam MG (2014) Insights into the structure and architecture of the CCR4-NOT complex. Front Genet 5:137

    PubMed  PubMed Central  Google Scholar 

  • Zhang L, Tran NT, Su H, Wang R, Lu Y, Tang H, Aoyagi S, Guo A, Khodadadi-Jamayran A, Zhou D, Qian K, Hricik T, Cote J, Han X, Zhou W, Laha S, Abdel-Wahab O, Levine RL, Raffel G, Liu Y, Chen D, Li H, Townes T, Wang H, Deng H, Zheng YG, Leslie C, Luo M, Zhao X (2015) Cross-talk between PRMT1-mediated methylation and ubiquitylation on RBM15 controls RNA splicing. Elife 4:e07938

    PubMed  PubMed Central  Google Scholar 

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Correspondence to Martine A. Collart .

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Collart, M.A., Panasenko, O.O. (2017). The Ccr4-Not Complex: Architecture and Structural Insights. In: Harris, J., Marles-Wright, J. (eds) Macromolecular Protein Complexes. Subcellular Biochemistry, vol 83. Springer, Cham. https://doi.org/10.1007/978-3-319-46503-6_13

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