MicroRNA mir-346 targets the 5′-untranslated region of receptor-interacting protein 140 (RIP140) mRNA and up-regulates its protein expression

Nien Pei Tsai, Yu-Lung Lin, Li-Na Wei

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

RIP140 (receptor-interacting protein 140) is a transcriptional corepressor 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 RIP140mRNAin mouse brain and P19 cells.A target sequence for miRNA(microRNA)mir-346was found in the 5′UTR (5′-untranslated region) of RIP140 mRNA; this miRNA is also expressed endogenously in mouse brain and P19 cells. Gainand 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 mir-346 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.

Original languageEnglish (US)
Pages (from-to)411-418
Number of pages8
JournalBiochemical Journal
Volume424
Issue number3
DOIs
StatePublished - Dec 15 2009

Keywords

  • 5′-untranslated region (5′UTR)
  • Argonaute 2
  • Brain
  • Mir-346
  • Receptor-interacting protein 140 (RIP140)
  • Translation regulation

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