MicroRNA mir-346 targets the 5'-untranslated region of receptor-interacting protein 140 (RIP140) mRNA and up-regulates its protein expression.
RIP140 (receptor-interacting protein 140) is a transcriptional co-repressor that regulates diverse genes such as those responsive to hormones and involved in metabolic processes. The expression of RIP140 is regulated by multiple hormonal activities in adipose tissue and cancer cell lines. However, it is unclear whether and how RIP140 is regulated post-transcriptionally. Using 5'RACE (rapid amplification of 5' cDNA ends), we have identified a novel 5' splice variant of RIP140 mRNA in mouse brain and P19 cells. A target sequence for miRNA (microRNA) mir-346 was found in the 5'UTR (5'-untranslated region) of RIP140 mRNA; this miRNA is also expressed endogenously in mouse brain and P19 cells. Gain- and loss-of-function studies demonstrated that mir-346 elevates RIP140 protein levels by facilitating association of its mRNA with the polysome fraction. Furthermore, the activity of mir346 does not require Ago-2 (Argonaute 2). The expression of mir-346 enhances the gene repressive activity of RIP140. This is the first report demonstrating post-transcriptional regulation of RIP140 mRNA, involving the enhancing effect of a specific miRNA that targets RIP140's 5'UTR.
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Nien-Pei
NP
Tsai
Ya-Lun
YL
Lin
Li-Na
LN
Wei
D020121:5' Untranslated Regions / Q000235:genetics*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D060565:Argonaute Proteins; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000078723:Nuclear Receptor Interacting Protein 1; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D020121:5' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; C526735:Ago2 protein, mouse; D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; C546336:MIRN346 microRNA, mouse; D035683:MicroRNAs; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D012333:RNA, Messenger