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Title: MicroRNA-340-mediated degradation of microphthalmia-associated transcription factor (MITF) mRNA is inhibited by coding region determinant-binding protein (CRD-BP).

Authors: Goswami, Srikanta; Tarapore, Rohinton S; Poenitzsch Strong, Ashley M; TeSlaa, Jessica J; Grinblat, Yevgenya; Setaluri, Vijayasaradhi; Spiegelman, Vladimir S

Published In J Biol Chem, (2015 Jan 02)

Abstract: Alternative cleavage and polyadenylation generates multiple transcript variants producing mRNA isoforms with different length 3'-UTRs. Alternative cleavage and polyadenylation enables differential post-transcriptional regulation 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. This central transcription factor is also implicated in melanoma development. Here, we show that melanoma cells favor the expression of MITF mRNA with a shorter 3'-UTR. We also establish that this isoform is regulated by a micro RNA (miRNA/miR), miR-340. miR-340 interacts with two of its target sites on the MITF 3'-UTR, causing mRNA degradation as well as decreased expression and activity of MITF. Conversely, the RNA-binding protein, coding region determinant-binding protein, was 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 the stabilization of MITF transcripts, elevated expression, and transcriptional activity of MITF. This regulatory interplay between RNA-binding protein and miRNA highlights an important mechanism for the regulation of MITF in melanocytes and malignant melanomas.

PubMed ID: 25414259 Exiting the NIEHS site

MeSH Terms: 3' Untranslated Regions*; Base Sequence; Cell Line, Tumor; Cell Proliferation; Cell Survival; Gene Expression Regulation, Neoplastic*; HEK293 Cells; Humans; Melanocytes/metabolism*; Melanocytes/pathology; MicroRNAs/genetics*; MicroRNAs/metabolism; Microphthalmia-Associated Transcription Factor/genetics*; Microphthalmia-Associated Transcription Factor/metabolism; Molecular Sequence Data; Protein Isoforms/genetics; Protein Isoforms/metabolism; RNA Stability; RNA-Binding Proteins/genetics*; RNA-Binding Proteins/metabolism; Signal Transduction

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