Uncoupling of expression of an intronic microRNA and its myosin host gene by exon skipping.
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.
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Matthew L
ML
Bell
Massimo
M
Buvoli
Leslie A
LA
Leinwand
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D024722:Cardiac Myosins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D018389:Codon, Nonsense; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D007438:Introns / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics* / Q000378:metabolism; D055755:SOXD Transcription Factors / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014018:Tissue Distribution; D015027:Zebrafish
D018389:Codon, Nonsense; C548683:MIRN499 microRNA, human; C501641:MYH7 protein, human; D035683:MicroRNAs; D020033:Protein Isoforms; D055755:SOXD Transcription Factors; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains