Home LiteratureArticle Details
PMID: 21203959 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

The structural basis for deadenylation by the CCR4-NOT complex.

Protein & cell ·Vol. 1 ·No. 5 ·2010-05-00 ·Pages 443-52

Bartlam M, Yamamoto T

Abstract

The CCR4-NOT complex is a highly conserved, multifunctional machinery controlling mRNA metabolism. Its components have been implicated in several aspects of mRNA and protein expression, including transcription initiation, elongation, mRNA degradation, ubiquitination, and protein modification. In this review, we will focus on the role of the CCR4-NOT complex in mRNA degradation. The complex contains two types of deadenylase enzymes, one belonging to the DEDD-type family and one belonging to the EEP-type family, which shorten the poly(A) tails of mRNA. We will review the present state of structure-function analyses into the CCR4-NOT deadenylases and summarize current understanding of their roles in mRNA degradation. We will also review structural and functional work on the Tob/BTG family of proteins, which are known to interact with the CCR4-NOT complex and which have been reported to suppress deadenylase activity in vitro.

MeSH Terms
Animals Humans Multiprotein Complexes/chemistry,genetics,metabolism Protein Conformation RNA, Messenger/genetics,metabolism Transcription Factors/chemistry,genetics,metabolism
Chemicals
CNOT1 protein, human Multiprotein Complexes RNA, Messenger Transcription Factors
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Bartlam Mark
Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin 300071, China. [email protected]
Yamamoto Tadashi
References (60)
60 references, click to expand
  1. Association of distinct yeast Not2 functional domains with components of Gcn5 histone acetylase and Ccr4 transcriptional regulatory complexes.
    EMBO J. 1998 Nov 16;17(22):6714-22 PMID: 9822614
  2. Identification of four families of yCCR4- and Mg2+-dependent endonuclease-related proteins in higher eukaryotes, and characterization of orthologs of yCCR4 with a conserved leucine-rich repeat essential for hCAF1/hPOP2 binding.
    BMC Genomics. 2001;2:9 PMID: 11747467
  3. Identification of multiple RNA features that influence CCR4 deadenylation activity.
    J Biol Chem. 2003 Apr 25;278(17):14949-55 PMID: 12590136
  4. Crystal structures of human BTG2 and mouse TIS21 involved in suppression of CAF1 deadenylase activity.
    Nucleic Acids Res. 2008 Dec;36(21):6872-81 PMID: 18974182
  5. Cloning of the mouse BTG3 gene and definition of a new gene family (the BTG family) involved in the negative control of the cell cycle.
    Leukemia. 1997 Mar;11(3):370-5 PMID: 9067576
  6. Ubiquitin-conjugating enzymes UBC4 and UBC5 mediate selective degradation of short-lived and abnormal proteins.
    EMBO J. 1990 Feb;9(2):543-50 PMID: 2154373
  7. Functionally unrelated signalling proteins contain a fold similar to Mg2+-dependent endonucleases.
    Trends Biochem Sci. 2000 Jun;25(6):272-3 PMID: 10838565
  8. Interaction of BTG1 and p53-regulated BTG2 gene products with mCaf1, the murine homolog of a component of the yeast CCR4 transcriptional regulatory complex.
    J Biol Chem. 1998 Aug 28;273(35):22563-9 PMID: 9712883
  9. The transcription factor associated Ccr4 and Caf1 proteins are components of the major cytoplasmic mRNA deadenylase in Saccharomyces cerevisiae.
    Cell. 2001 Feb 9;104(3):377-86 PMID: 11239395
  10. Ccr4p is the catalytic subunit of a Ccr4p/Pop2p/Notp mRNA deadenylase complex in Saccharomyces cerevisiae.
    EMBO J. 2002 Mar 15;21(6):1427-36 PMID: 11889048
  11. Human Ccr4-Not complexes contain variable deadenylase subunits.
    Biochem J. 2009 Aug 27;422(3):443-53 PMID: 19558367
  12. Reconstitution, activities, and structure of the eukaryotic RNA exosome.
    Cell. 2006 Dec 15;127(6):1223-37 PMID: 17174896
  13. Saccharomyces cerevisiae Ccr4-not complex contributes to the control of Msn2p-dependent transcription by the Ras/cAMP pathway.
    Mol Microbiol. 2002 Feb;43(4):1023-37 PMID: 11929548
  14. Purification and characterization of the 1.0 MDa CCR4-NOT complex identifies two novel components of the complex.
    J Mol Biol. 2001 Dec 7;314(4):683-94 PMID: 11733989
  15. Cnot7-null mice exhibit high bone mass phenotype and modulation of BMP actions.
    J Bone Miner Res. 2007 Aug;22(8):1217-23 PMID: 17451368
  16. Multifunctional deadenylase complexes diversify mRNA control.
    Nat Rev Mol Cell Biol. 2008 Apr;9(4):337-44 PMID: 18334997
  17. The CCR4-NOT complex plays diverse roles in mRNA metabolism.
    Prog Nucleic Acid Res Mol Biol. 2003;73:221-50 PMID: 12882519
  18. Formation of mRNA 3' ends in eukaryotes: mechanism, regulation, and interrelationships with other steps in mRNA synthesis.
    Microbiol Mol Biol Rev. 1999 Jun;63(2):405-45 PMID: 10357856
  19. Tc, an unusual promoter element required for constitutive transcription of the yeast HIS3 gene.
    Mol Cell Biol. 1990 Sep;10(9):4447-55 PMID: 2201891
  20. The structure of the C4C4 ring finger of human NOT4 reveals features distinct from those of C3HC4 RING fingers.
    J Biol Chem. 2001 Mar 30;276(13):10185-90 PMID: 11087754
  21. Isolation and characterization of human orthologs of yeast CCR4-NOT complex subunits.
    Nucleic Acids Res. 2000 Feb 1;28(3):809-17 PMID: 10637334
  22. BTG2 antiproliferative protein interacts with the human CCR4 complex existing in vivo in three cell-cycle-regulated forms.
    J Cell Sci. 2003 Jul 15;116(Pt 14):2929-36 PMID: 12771185
  23. Structural basis for the antiproliferative activity of the Tob-hCaf1 complex.
    J Biol Chem. 2009 May 8;284(19):13244-55 PMID: 19276069
  24. CCR4-associated factor CAF1 is an essential factor for spermatogenesis.
    Mol Cell Biol. 2004 Jul;24(13):5808-20 PMID: 15199137
  25. Characterization of NOT5 that encodes a new component of the Not protein complex.
    Gene. 1998 Jan 19;207(1):61-9 PMID: 9511744
  26. The inositol polyphosphate 5-phosphatases and the apurinic/apyrimidinic base excision repair endonucleases share a common mechanism for catalysis.
    J Biol Chem. 2000 Nov 24;275(47):37055-61 PMID: 10962003
  27. Identification of a ubiquitin-protein ligase subunit within the CCR4-NOT transcription repressor complex.
    EMBO J. 2002 Feb 1;21(3):355-64 PMID: 11823428
  28. The Ccr4-not complex and yTAF1 (yTaf(II)130p/yTaf(II)145p) show physical and functional interactions.
    Mol Cell Biol. 2002 Oct;22(19):6735-49 PMID: 12215531
  29. The CCR4 and CAF1 proteins of the CCR4-NOT complex are physically and functionally separated from NOT2, NOT4, and NOT5.
    Mol Cell Biol. 1999 Oct;19(10):6642-51 PMID: 10490603
  30. The CCR4 protein from Saccharomyces cerevisiae contains a leucine-rich repeat region which is required for its control of ADH2 gene expression.
    Genetics. 1992 Dec;132(4):951-62 PMID: 1459446
  31. The BTG2 protein is a general activator of mRNA deadenylation.
    EMBO J. 2008 Apr 9;27(7):1039-48 PMID: 18337750
  32. 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. 2001 Mar 9;276(10):7541-8 PMID: 11113136
  33. Functional organization of the yeast proteome by systematic analysis of protein complexes.
    Nature. 2002 Jan 10;415(6868):141-7 PMID: 11805826
  34. Concerted action of poly(A) nucleases and decapping enzyme in mammalian mRNA turnover.
    Nat Struct Mol Biol. 2005 Dec;12(12):1054-63 PMID: 16284618
  35. Human carbon catabolite repressor protein (CCR4)-associative factor 1: cloning, expression and characterization of its interaction with the B-cell translocation protein BTG1.
    Biochem J. 1998 Dec 1;336 ( Pt 2):471-81 PMID: 9820826
  36. Functional interaction of CCR4-NOT proteins with TATAA-binding protein (TBP) and its associated factors in yeast.
    Genetics. 2000 Jul;155(3):1045-54 PMID: 10880468
  37. Interaction of antiproliferative protein Tob with the CCR4-NOT deadenylase complex.
    Cancer Sci. 2008 Apr;99(4):755-61 PMID: 18377426
  38. Interplay of positive and negative regulators in transcription initiation by RNA polymerase II holoenzyme.
    Mol Cell Biol. 1998 Aug;18(8):4455-62 PMID: 9671455
  39. Dhh1p, a putative RNA helicase, associates with the general transcription factors Pop2p and Ccr4p from Saccharomyces cerevisiae.
    Genetics. 1998 Feb;148(2):571-9 PMID: 9504907
  40. RNA quality control in eukaryotes.
    Cell. 2007 Nov 16;131(4):660-8 PMID: 18022361
  41. Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta.
    Nat Genet. 2004 May;36(5):528-33 PMID: 15107851
  42. X-ray structure and activity of the yeast Pop2 protein: a nuclease subunit of the mRNA deadenylase complex.
    EMBO Rep. 2003 Dec;4(12):1150-5 PMID: 14618157
  43. The eukaryotic Ccr4-not complex: a regulatory platform integrating mRNA metabolism with cellular signaling pathways?
    Prog Nucleic Acid Res Mol Biol. 2004;77:289-322 PMID: 15196896
  44. CCR4 is a glucose-regulated transcription factor whose leucine-rich repeat binds several proteins important for placing CCR4 in its proper promoter context.
    Mol Cell Biol. 1994 Jul;14(7):4522-31 PMID: 8007957
  45. Identification of a mouse protein whose homolog in Saccharomyces cerevisiae is a component of the CCR4 transcriptional regulatory complex.
    Mol Cell Biol. 1995 Jul;15(7):3487-95 PMID: 7791755
  46. DBF2, a cell cycle-regulated protein kinase, is physically and functionally associated with the CCR4 transcriptional regulatory complex.
    EMBO J. 1997 Sep 1;16(17):5289-98 PMID: 9311989
  47. Interaction between Not1p, a component of the Ccr4-not complex, a global regulator of transcription, and Dhh1p, a putative RNA helicase.
    J Biol Chem. 2002 Jan 25;277(4):2835-42 PMID: 11696541
  48. NOT1(CDC39), NOT2(CDC36), NOT3, and NOT4 encode a global-negative regulator of transcription that differentially affects TATA-element utilization.
    Genes Dev. 1994 Mar 1;8(5):525-37 PMID: 7926748
  49. Depletion of mammalian CCR4b deadenylase triggers elevation of the p27Kip1 mRNA level and impairs cell growth.
    Mol Cell Biol. 2007 Jul;27(13):4980-90 PMID: 17452450
  50. CDC39, an essential nuclear protein that negatively regulates transcription and differentially affects the constitutive and inducible HIS3 promoters.
    EMBO J. 1993 Jan;12(1):177-86 PMID: 8428577
  51. The NOT proteins are part of the CCR4 transcriptional complex and affect gene expression both positively and negatively.
    EMBO J. 1998 Feb 16;17(4):1096-106 PMID: 9463387
  52. DBF2 protein kinase binds to and acts through the cell cycle-regulated MOB1 protein.
    Mol Cell Biol. 1998 Apr;18(4):2100-7 PMID: 9528782
  53. Relationships of the antiproliferative proteins BTG1 and BTG2 with CAF1, the human homolog of a component of the yeast CCR4 transcriptional complex: involvement in estrogen receptor alpha signaling pathway.
    J Biol Chem. 2001 Mar 30;276(13):9640-8 PMID: 11136725
  54. TBP-associated factors are not generally required for transcriptional activation in yeast.
    Nature. 1996 Sep 12;383(6596):188-91 PMID: 8774887
  55. The leukemia-associated protein Btg1 and the p53-regulated protein Btg2 interact with the homeoprotein Hoxb9 and enhance its transcriptional activation.
    J Biol Chem. 2000 Jan 7;275(1):147-53 PMID: 10617598
  56. Interaction of PRMT1 with BTG/TOB proteins in cell signalling: molecular analysis and functional aspects.
    Genes Cells. 2002 Jan;7(1):29-39 PMID: 11856371
  57. CCR4, a 3'-5' poly(A) RNA and ssDNA exonuclease, is the catalytic component of the cytoplasmic deadenylase.
    EMBO J. 2002 Mar 15;21(6):1414-26 PMID: 11889047
  58. Genome wide expression analysis of the CCR4-NOT complex indicates that it consists of three modules with the NOT module controlling SAGA-responsive genes.
    Mol Genet Genomics. 2008 Apr;279(4):323-37 PMID: 18214544
  59. Global control of gene expression in yeast by the Ccr4-Not complex.
    Gene. 2003 Aug 14;313:1-16 PMID: 12957374
  60. The activity and selectivity of fission yeast Pop2p are affected by a high affinity for Zn2+ and Mn2+ in the active site.
    RNA. 2009 May;15(5):850-61 PMID: 19307292
Article Info
Journal
Protein & cell
Abbr.
Protein Cell
ISSN
1674-8018
DOI
10.1007/s13238-010-0060-8
Email
[email protected]
Published
2010-05-00
Epub
2010-00-04
Pages
443-52
Language
English
Region
Germany
NLM ID
101532368
PMCID
PMC4875137
Subset
IM
External Links
PubMed source DOI: 10.1007/s13238-010-0060-8 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2