title: RNA-binding protein HuR and the members of the miR-200 family play an unconventional role in the regulation of c-Jun mRNA.
abstract: Post-transcriptional gene regulation is a fundamental step for coordinating cellular response in a variety of processes. RNA-binding proteins (RBPs) and microRNAs (miRNAs) are the most important factors responsible for this regulation. Here we report that different components of the miR-200 family are involved in c-Jun mRNA regulation with the opposite effect. While miR-200b inhibits c-Jun protein production, miR-200a tends to increase the JUN amount through a stabilization of its mRNA. This action is dependent on the presence of the RBP HuR that binds the 3'UTR of c-Jun mRNA in a region including the mir-200a binding site. The position of the binding site is fundamental; by mutating this site, we demonstrate that the effect is not micro-RNA specific. These results indicate that miR-200a triggers a microRNA-mediated stabilization of c-Jun mRNA, promoting the binding of HuR with c-Jun mRNA. This is the first example of a positive regulation exerted by a microRNA on an important oncogene in proliferating cells.
authors.affiliation: Dipartimento di Biologia e Biotecnologie, Università "Sapienza," 00185 Rome, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Del Vecchio
authors.affiliation: Dipartimento di Biologia e Biotecnologie, Università "Sapienza," 00185 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Vito
authors.affiliation: Bioinformatics Group, Department of Computer Science, Albert-Ludwigs-University Freiburg, 79110 Freiburg, Germany.
authors.forename: Sita J
authors.initials: SJ
authors.lastname: Saunders
authors.affiliation: Dipartimento di Biologia e Biotecnologie, Università "Sapienza," 00185 Rome, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Risi
authors.affiliation: IBPM-CNR, 00185 Rome, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Mannironi
authors.affiliation: Dipartimento di Biologia e Biotecnologie, Università "Sapienza," 00185 Rome, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Bozzoni
authors.affiliation: Dipartimento di Biologia e Biotecnologie, Università "Sapienza," 00185 Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Presutti
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D000067780:ELAV-Like Protein 1 / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases
keywords: HuR; c-Jun; mRNA stability; miRNA