title: Control of translation and miRNA-dependent repression by a novel poly(A) binding protein, hnRNP-Q.
abstract: Translation control often operates via remodeling of messenger ribonucleoprotein particles. The poly(A) binding protein (PABP) simultaneously interacts with the 3' poly(A) tail of the mRNA and the eukaryotic translation initiation factor 4G (eIF4G) to stimulate translation. PABP also promotes miRNA-dependent deadenylation and translational repression of target mRNAs. We demonstrate that isoform 2 of the mouse heterogeneous nuclear protein Q (hnRNP-Q2/SYNCRIP) binds poly(A) by default when PABP binding is inhibited. In addition, hnRNP-Q2 competes with PABP for binding to poly(A) in vitro. Depleting hnRNP-Q2 from translation extracts stimulates cap-dependent and IRES-mediated translation that is dependent on the PABP/poly(A) complex. Adding recombinant hnRNP-Q2 to the extracts inhibited translation in a poly(A) tail-dependent manner. The displacement of PABP from the poly(A) tail by hnRNP-Q2 impaired the association of eIF4E with the 5' m(7)G cap structure of mRNA, resulting in the inhibition of 48S and 80S ribosome initiation complex formation. In mouse fibroblasts, silencing of hnRNP-Q2 stimulated translation. In addition, hnRNP-Q2 impeded let-7a miRNA-mediated deadenylation and repression of target mRNAs, which require PABP. Thus, by competing with PABP, hnRNP-Q2 plays important roles in the regulation of global translation and miRNA-mediated repression of specific mRNAs.
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Svitkin
authors.forename: Akiko
authors.initials: A
authors.lastname: Yanagiya
authors.forename: Alexey E
authors.initials: AE
authors.lastname: Karetnikov
authors.forename: Tommy
authors.initials: T
authors.lastname: Alain
authors.forename: Marc R
authors.initials: MR
authors.lastname: Fabian
authors.forename: Arkady
authors.initials: A
authors.lastname: Khoutorsky
authors.forename: Sandra
authors.initials: S
authors.lastname: Perreault
authors.forename: Ivan
authors.initials: I
authors.lastname: Topisirovic
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D000818:Animals; D001665:Binding Sites; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006367:HeLa Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D035683:MicroRNAs; C486049:Syncrip protein, mouse; C542687:mirnlet7 microRNA, mouse