title: GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA targets.
abstract: miRNAs are posttranscriptional regulators of gene expression that associate with Argonaute and GW182 proteins to repress translation and/or promote mRNA degradation. miRNA-mediated mRNA degradation is initiated by deadenylation, although it is not known whether deadenylases are recruited to the mRNA target directly or by default, as a consequence of a translational block. To answer this question, we performed a screen for potential interactions between the Argonaute and GW182 proteins and subunits of the two cytoplasmic deadenylase complexes. We found that human GW182 proteins recruit the PAN2-PAN3 and CCR4-CAF1-NOT deadenylase complexes through direct interactions with PAN3 and NOT1, respectively. These interactions are critical for silencing and are conserved in D. melanogaster. Our findings reveal that GW182 proteins provide a docking platform through which deadenylase complexes gain access to the poly(A) tail of miRNA targets to promote their deadenylation, and they further indicate that deadenylation is a direct effect of miRNA regulation.
authors: Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tübingen, Germany.
authors: Joerg E
authors: JE
authors: Braun
authors: Eric
authors: E
authors: Huntzinger
authors: Maria
authors: M
authors: Fauser
authors: Elisa
authors: E
authors: Izaurralde
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D005095:Exoribonucleases / Q000378:metabolism; D020868:Gene Silencing; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D011061:Poly A / Q000378:metabolism; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D054398:Receptors, CCR4 / Q000378:metabolism; D056505:Retinoblastoma-Binding Protein 4 / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C515354:CCR4 protein, human; C528690:CNOT1 protein, human; C489780:CNOT8 protein, human; C110251:Caf1-55 protein, Drosophila; D002352:Carrier Proteins; D029721:Drosophila Proteins; C513405:Gw protein, Drosophila; D035683:MicroRNAs; C568695:NOT1 protein, Drosophila; C568693:PAN3 protein, human; D016601:RNA-Binding Proteins; D054398:Receptors, CCR4; D056505:Retinoblastoma-Binding Protein 4; D014157:Transcription Factors; D011061:Poly A; C501437:CCR4 protein, Drosophila; D005095:Exoribonucleases; C568694:PAN2 protein, Drosophila; D012260:Ribonucleases; C551828:PAN2 protein, human