title: C2ORF29/CNOT11 and CNOT10 form a new module of the CCR4-NOT complex.
abstract: The CCR4-NOT complex was originally identified and its composition and organization characterized in the yeast Saccharomyces cerevisiae. It was first suggested to participate in transcription regulation, but since then it has become clear that it plays a key role in mRNA decay in all eukaryotes, thereby contributing importantly to gene expression regulation. Hence, the mammalian CCR4-NOT complex was recently shown to participate in miRNA-mediated mRNA repression. A better characterization of the composition and organization of this complex in higher eukaryotes is thus warranted. Purifications of the CCR4-NOT complex, performed by others and us, suggest that the protein of unknown function C2ORF29 is associated with this assembly. We demonstrate here that C2ORF29 is indeed a bona fide subunit of the human CCR4-NOT complex and propose to rename it CNOT11. In addition, we show that CNOT11 interacts with the first amino acids of CNOT1 and with CNOT10 and is required for the association of CNOT10 with the CCR4-NOT complex. Thus, the human CCR4-NOT complex possesses in addition to the CCR4-CAF1 deadenylase module and to the NOT module, a module composed of CNOT10 and CNOT11 that interacts with the N-terminal part of CNOT1. Phylogenetic analyses indicate that the CNOT10/CNOT11 module is conserved in all eukaryotes except fungi.
authors.affiliation: Equipe Labellisée La Ligue, Institut de Génétique et de Biologie Moléculaire et Cellulaire IGBMC, Centre National de Recherche Scientifique CNRS, UMR 7104, Institut National de Santé et de Recherche Médicale INSERM, U964, Université de Strasbourg, Illkirch, France. mauxion@igbmc.fr
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mauxion
authors.forename: Brigitte
authors.initials: B
authors.lastname: Prève
authors.forename: Bertrand
authors.initials: B
authors.lastname: Séraphin
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D025941:Protein Interaction Mapping; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C528690:CNOT1 protein, human; C489780:CNOT8 protein, human; D035683:MicroRNAs; D046912:Multiprotein Complexes; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors