Control of translation and miRNA-dependent repression by a novel poly(A) binding protein, hnRNP-Q

• Published in: PLoS biology Vol. 11; no. 5; p. e1001564
• Main Authors: Svitkin, Yuri V, Yanagiya, Akiko, Karetnikov, Alexey E, Alain, Tommy, Fabian, Marc R, Khoutorsky, Arkady, Perreault, Sandra, Topisirovic, Ivan, Sonenberg, Nahum
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.05.2013; Public Library of Science (PLoS)
• Subjects: Animals; Binding proteins; Binding Sites; Biology; Competition; Eukaryotic Initiation Factor-4E - genetics; Eukaryotic Initiation Factor-4E - metabolism; Experiments; Fibroblasts - metabolism; Genetic translation; HeLa Cells; Heterogeneous-Nuclear Ribonucleoproteins - genetics; Heterogeneous-Nuclear Ribonucleoproteins - metabolism; Humans; Medical research; Mice; MicroRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Physiological aspects; Proteins; RNA sequencing; Translations; Canada; Animals; Humans; MicroRNAs; Fibroblasts; Mice; HeLa Cells; Heterogeneous-Nuclear Ribonucleoproteins; Binding Sites; Eukaryotic Initiation Factor-4E
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.1001564

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.