A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance.
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.
van Rooij
Eva
E
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Quiat
Daniel
D
Johnson
Brett A
BA
Sutherland
Lillian B
LB
Qi
Xiaoxia
X
Richardson
James A
JA
Kelm
Robert J
RJ
Olson
Eric N
EN
D000818:Animals; D001483:Base Sequence; D024722:Cardiac Myosins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D024462:Myosin Type II / Q000235:genetics / Q000378:metabolism
D024722:Cardiac Myosins; D035683:MicroRNAs; D018995:Myosin Heavy Chains; D024462:Myosin Type II; C477830:MYH7b protein, human; C094239:MYH6 protein, human; C543978:Mirn208 microRNA, mouse; C483905:Myh14 protein, mouse