MicroRNA-340-mediated degradation of microphthalmia-associated transcription factor mRNA is inhibited by the coding region determinant-binding protein

Srikanta Goswami, Rohinton S. Tarapore, Jessica J. TeSlaa, Yevgenya Grinblat, Vijayasaradhi Setaluri, Vladimir S. Spiegelman

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Alternative cleavage and polyadenylation generate multiple transcript variants of mRNA isoforms with different length of 3′-untranslated region (UTR). Alternative cleavage and polyadenylation enable differential post-transcriptional regulation of transcripts via the availability of different cis-acting elements in 3′-UTRs. Microphthalmia-associated transcription factor (MITF) is a master regulator of melanocyte development and melanogenesis. It has also been implicated in melanoma development. Here we show that melanoma cells favor the expression of MITF mRNA with shorter 3′-UTR. This isoform of mRNA is regulated by microRNA, miR-340. miR-340 interacts with two of its target sites on the 3′-UTR of MITF mRNA, causingmRNA degradation and decreased expression and activity of MITF. On the other hand, the RNA-binding protein coding region determinant-binding protein, shown to be highly expressed in melanoma, directly binds to the 3′-UTR of MITF mRNA and prevents the binding of miR-340 to its target sites, resulting in stabilization of the MITF transcript and elevated expression and transcriptional activity of MITF. This interplay between RNA-binding protein and miRNA describes the important mechanism of regulation of MITF in melanocytes and malignant melanomas.

Original languageEnglish (US)
Pages (from-to)20532-20540
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number27
DOIs
StatePublished - Jul 2 2010

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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