title: The interactions of GW182 proteins with PABP and deadenylases are required for both translational repression and degradation of miRNA targets.
abstract: Animal miRNAs silence the expression of mRNA targets through translational repression, deadenylation and subsequent mRNA degradation. Silencing requires association of miRNAs with an Argonaute protein and a GW182 family protein. In turn, GW182 proteins interact with poly(A)-binding protein (PABP) and the PAN2-PAN3 and CCR4-NOT deadenylase complexes. These interactions are required for the deadenylation and decay of miRNA targets. Recent studies have indicated that miRNAs repress translation before inducing target deadenylation and decay; however, whether translational repression and deadenylation are coupled or represent independent repressive mechanisms is unclear. Another remaining question is whether translational repression also requires GW182 proteins to interact with both PABP and deadenylases. To address these questions, we characterized the interaction of Drosophila melanogaster GW182 with deadenylases and defined the minimal requirements for a functional GW182 protein. Functional assays in D. melanogaster and human cells indicate that miRNA-mediated translational repression and degradation are mechanistically linked and are triggered through the interactions of GW182 proteins with PABP and deadenylases.
authors.affiliation: Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tübingen, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Huntzinger
authors.forename: Duygu
authors.initials: D
authors.lastname: Kuzuoglu-Öztürk
authors.forename: Joerg E
authors.initials: JE
authors.lastname: Braun
authors.forename: Ana
authors.initials: A
authors.lastname: Eulalio
authors.forename: Lara
authors.initials: L
authors.lastname: Wohlbold
authors.forename: Elisa
authors.initials: E
authors.lastname: Izaurralde
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D054730:Protein Interaction Domains and Motifs; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry; D012260:Ribonucleases / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry
chemical_list: C528690:CNOT1 protein, human; D002352:Carrier Proteins; D029721:Drosophila Proteins; C513405:Gw protein, Drosophila; D035683:MicroRNAs; C568695:NOT1 protein, Drosophila; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C540399:TNRC6C protein, human; D014157:Transcription Factors; D012260:Ribonucleases; C445084:mRNA deadenylase