MicroRNA-340-Mediated Degradation of Microphthalmia-Associated Transcription Factor (MITF) mRNA is Inhibited by Coding Region Determinant Binding Protein (CRD-BP) [RNA]
November 20th, 2014 by Goswami, S., Tarapore, R. S., Poenitzsch Strong, A. M., TeSlaa, J. J., Grinblat, Y., Setaluri, V., Spiegelman, V. S.
Alternative cleavage and polyadenylation (APA) generates multiple transcript variants producing mRNA isoforms with different length 3'-UTRs. APA 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 melanoma cells favor the expression of MITF mRNA with a shorter 3'-UTR. We also establish that this isoform is regulated by microRNA (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 (RBP), Coding region determinant binding protein (CRD-BP) 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.