RNA-binding protein HuR and the members of the miR-200 family play an unconventional role in the regulation of c-Jun mRNA.
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.
['Del Vecchio|Giorgia|G|', 'De Vito|Francesca|F|', 'Saunders|Sita J|SJ|', 'Risi|Adele|A|', 'Mannironi|Cecilia|C|', 'Bozzoni|Irene|I|', 'Presutti|Carlo|C|']
D020413:3' Untranslated Regions D001665:Binding Sites D000067780:ELAV-Like Protein 1 D057809:HEK293 Cells D006367:HeLa Cells D006801:Humans D048031:JNK Mitogen-Activated Protein Kinases D061986:MCF-7 Cells D035683:MicroRNAs D011485:Protein Binding D020871:RNA Stability D012333:RNA, Messenger
HuR c-Jun miRNA mRNA stability