title: miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT.
abstract: miRNAs recruit the miRNA-induced silencing complex (miRISC), which includes Argonaute and GW182 as core proteins. GW182 proteins effect translational repression and deadenylation of target mRNAs. However, the molecular mechanisms of GW182-mediated repression remain obscure. We show here that human GW182 independently interacts with the PAN2-PAN3 and CCR4-NOT deadenylase complexes. Interaction of GW182 with CCR4-NOT is mediated by two newly discovered phylogenetically conserved motifs. Although either motif is sufficient to bind CCR4-NOT, only one of them can promote processive deadenylation of target mRNAs. Thus, GW182 serves as both a platform that recruits deadenylases and as a deadenylase coactivator that facilitates the removal of the poly(A) tail by CCR4-NOT.
authors: Department of Biochemistry, McGill University, Montreal, Canada.
authors: Marc R
authors: MR
authors: Fabian
authors: Maja K
authors: MK
authors: Cieplak
authors: Filipp
authors: F
authors: Frank
authors: Masahiro
authors: M
authors: Morita
authors: Jonathan
authors: J
authors: Green
authors: Tharan
authors: T
authors: Srikumar
authors: Bhushan
authors: B
authors: Nagar
authors: Tadashi
authors: T
authors: Yamamoto
authors: Brian
authors: B
authors: Raught
authors: Thomas F
authors: TF
authors: Duchaine
authors: Nahum
authors: N
authors: Sonenberg
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D001324:Autoantigens; C528690:CNOT1 protein, human; D002352:Carrier Proteins; D035683:MicroRNAs; D046912:Multiprotein Complexes; C568693:PAN3 protein, human; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; C465663:TNRC6A protein, human; D014157:Transcription Factors; D005095:Exoribonucleases; C551828:PAN2 protein, human