Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Alternative Splicing*
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Amino Acid Sequence
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Animals
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Cardiac Myosins / genetics*
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Cardiac Myosins / metabolism
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Cell Line
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Codon, Nonsense
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Exons*
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Gene Expression Regulation
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Humans
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Introns / genetics*
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Mice
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Mice, Inbred C57BL
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Molecular Sequence Data
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Myosin Heavy Chains / genetics*
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Myosin Heavy Chains / metabolism
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Protein Isoforms / genetics*
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Protein Isoforms / metabolism
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SOXD Transcription Factors / genetics
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SOXD Transcription Factors / metabolism
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Sequence Alignment
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Tissue Distribution
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Zebrafish
Substances
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Codon, Nonsense
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MIRN499 microRNA, human
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MYH7 protein, human
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MicroRNAs
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Protein Isoforms
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SOXD Transcription Factors
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Cardiac Myosins
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Myosin Heavy Chains