title: The ribosomal protein RACK1 is required for microRNA function in both C. elegans and humans.
abstract: Despite the importance of microRNAs (miRNAs) in gene regulation, it is unclear how the miRNA-Argonaute complex--or miRNA-induced silencing complex (miRISC)--can regulate the translation of their targets in such diverse ways. We demonstrate here a direct interaction between the miRISC and the ribosome by showing that a constituent of the eukaryotic 40S subunit, receptor for activated C-kinase (RACK1), is important for miRNA-mediated gene regulation in animals. In vivo studies demonstrate that RACK1 interacts with components of the miRISC in nematodes and mammals. In both systems, the alteration of RACK1 expression alters miRNA function and impairs the association of the miRNA complex with the translating ribosomes. Our data indicate that RACK1 can contribute to the recruitment of miRISC to the site of translation, and support a post-initiation mode of miRNA-mediated gene repression.
authors.affiliation: Laval University Cancer Research Centre, Hôtel-Dieu de Québec, 9 McMahon Street, Quebec City, Québec G1R 2J6, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jannot
authors.forename: Sarah
authors.initials: S
authors.lastname: Bajan
authors.forename: Nellie J
authors.initials: NJ
authors.lastname: Giguère
authors.forename: Samir
authors.initials: S
authors.lastname: Bouasker
authors.forename: Isabelle H
authors.initials: IH
authors.lastname: Banville
authors.forename: Sandra
authors.initials: S
authors.lastname: Piquet
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Hutvagner
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Simard
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011132:Polyribosomes / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D035683:MicroRNAs; D009363:Neoplasm Proteins; C556161:RACK-1 protein, C elegans; C419368:RACK1 protein, human; D034743:RNA-Induced Silencing Complex; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D019204:GTP-Binding Proteins