A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance.

By Eva van Rooij, Daniel Quiat, Brett A. Johnson, L. Sutherland, X. Qi, J. Richardson, R. Kelm, E. Olson. Developmental Cell, 2009

977 citations recorded by the source corpus.

Myosin is the primary regulator of muscle strength and contractility. Here we show that three myosin genes, Myh6, Myh7, and Myh7b, encode related intronic microRNAs (miRNAs), which, in turn, control muscle myosin content, myofiber identity, and muscle performance. Within the adult heart, the Myh6 gene, encoding a fast myosin, coexpresses miR-208a, which regulates the expression of two slow myosins and their intronic miRNAs, Myh7/miR-208b and Myh7b/miR-499, respectively. miR-208b and miR-499 play redundant roles in the specification of muscle fiber identity by activating slow and repressing fast myofiber gene programs. The actions of these miRNAs are mediated in part by a collection of transcriptional repressors of slow myofiber genes. These findings reveal that myosin genes not only encode the major contractile proteins of muscle, but act more broadly to influence muscle function by encoding a network of intronic miRNAs that control muscle gene expression and performance.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2d1f978fd7046fb2787d13ed7b23fbcdd2a158a6

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Citations in the corpus

Fiber types in mammalian skeletal muscles. (2011, background): “The transcriptional repressors Pur and Sp3, which were previously shown to repress MyHC- /slow expression in mouse skeletal muscle (381), are also targets of miR-499 and miR-208b (817).”
MicroRNAs in stress signaling and human disease (2012, background): “…multiple aspects of embryonic development (Ventura et al., 2008), miR133a-1 and miR-133a-2, which together are required for appropriate cardiac and skeletal muscle development (Liu et al., 2008, 2011), and miR-208b and miR-499, which coregulate muscle fiber type identity (van Rooij et al., 2009).”
Metazoan MicroRNAs (2018, background): “1) miR-208b, miR-499 Reduced proportion of slow myofibers in skeletal muscle (van Rooij et al., 2009) miR-15/16/195/322/497 (vert.”
Satellite cells and the muscle stem cell niche. (2013, background): “Recent studies demonstrated that the specification of myosin expression is also regulated by intronic microRNAs within MyHC genes (545, 546).”
Development of microRNA therapeutics is coming of age (2014, background): “Shortly after the first report on miR-208a, it was discovered that the bMHC gene also contains an intronic miR-208 isoform, named miR-208b (van Rooij et al, 2009).”
A Micropeptide Encoded by a Putative Long Non-coding RNA Regulates Muscle Performance (2015, neutral): “Mice with a fast-toslow fiber type switch also show increased running performance (van Rooij et al., 2009).”
Exercise metabolism and the molecular regulation of skeletal muscle adaptation. (2013, background): “In mice overexpressing miR-499, a conversion of type II fibers to predominantly type I fibers is observed, which coincides with enhanced oxidative metabolism and improved treadmill running capacity (van Rooij et al., 2009).”