title: IMP-3 protects the mRNAs of cyclins D1 and D3 from GW182/AGO2-dependent translational repression.
abstract: IGF-2 mRNA binding protein 3 (IGF2BP3, IMP-3) is a well-known post-transcriptional regulatory factor of gene expression, mainly involved in embryonic development and oncogenesis. We have previously demonstrated that a subset of IMP-3 targets, such as the mRNAs of cyclins D1, D3 and G1, are positively regulated by IMP-3, and that this regulation depends on nuclear localization of IMP-3. In the present study, we show that as a first step following a knock-down of IMP-3, the protein levels of the cyclins rapidly decrease, while their mRNAs remain stable and associated with the polyribosomes, though not translated. We have elucidated the molecular mechanisms of this regulation, demonstrating that IMP-3 and its protein partners ILF3/NF90 and PTBP1 bind to the 3'UTRs of the cyclin mRNAs and protect them from the translational repression induced by miRNA-dependent recruitment of AGO2/GW182 complex in human cancer cells.
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, University Paris XI, University Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Deforzh
authors.affiliation: INSERM, UMR 866, Centre Georges François Leclerc, University of Bourgogne, Dijon, France.
authors.forename: Thaiz Rivera
authors.initials: TR
authors.lastname: Vargas
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, University Paris XI, University Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Jeremie
authors.initials: J
authors.lastname: Kropp
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, University Paris XI, University Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Vandamme
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, University Paris XI, University Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pinna
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), IBITECS, CEA, CNRS, University Paris XI, University Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Polesskaya
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism*; D001324:Autoantigens / Q000378:metabolism*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics*; D056743:Cyclin D3 / Q000096:biosynthesis / Q000235:genetics*; D056766:Cyclin G1 / Q000235:genetics; D000067780:ELAV-Like Protein 1 / Q000235:genetics; D039642:Eukaryotic Initiation Factors / Q000235:genetics; D006801:Humans; D050779:Nuclear Factor 90 Proteins / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C115848:AGO1 protein, human; C466422:AGO2 protein, human; D060565:Argonaute Proteins; D001324:Autoantigens; C530104:CCND1 protein, human; C534696:CCND3 protein, human; C534702:CCNG1 protein, human; D056743:Cyclin D3; D056766:Cyclin G1; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D039642:Eukaryotic Initiation Factors; C498780:IGF2BP3 protein, human; C429643:ILF3 protein, human; D050779:Nuclear Factor 90 Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C465663:TNRC6A protein, human; D019938:Cyclin D1