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Uncoupling of Expression of an Intronic MicroRNA and Its Myosin Host Gene by Exon Skipping

2010; Taylor & Francis; Volume: 30; Issue: 8 Linguagem: Inglês

10.1128/mcb.01370-09

1098-5549

Matthew Bell, Massimo Buvoli, Leslie A. Leinwand,

RNA Interference and Gene Delivery

The ancient MYH7b gene, expressed in striated muscle and brain, encodes a sarcomeric myosin and the intronic microRNA miR-499. We find that skipping of an exon introduces a premature termination codon in the transcript that downregulates MYH7b protein production without affecting microRNA expression. Among other genes, endogenous miR-499 targets the 3' untranslated region of the transcription factor Sox6, which in turn acts as a repressor of MYH7b transcriptional activity. Thus, concerted transcription and alternative splicing uncouple the level of expression of MYH7b and miR-499 when their coexpression is not required.