TY - JOUR
T1 - A Family of microRNAs Encoded by Myosin Genes Governs Myosin Expression and Muscle Performance
AU - van Rooij, Eva
AU - Quiat, Daniel
AU - Johnson, Brett A.
AU - Sutherland, Lillian B.
AU - Qi, Xiaoxia
AU - Richardson, James A.
AU - Kelm, Robert J.
AU - Olson, Eric N.
N1 - Funding Information:
We are grateful to John McAnally and John Shelton for experimental assistance. Work in Eric Olson's laboratory was supported by grants from the National Institutes of Health, the Donald W. Reynolds Cardiovascular Clinical Research Center, the Leducq Foundation, the Robert A. Welch Foundation, and the American Heart Association: Jon Holden DeHaan Foundation. E.V.R. was supported by grants from the American Heart Association. E.N.O. and E.V.R. hold equity in miRagen Therapeutics, which is developing miRNA-based therapies for muscle disease.
PY - 2009/11/17
Y1 - 2009/11/17
N2 - 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.
AB - 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.
KW - DEVBIO
KW - RNA
UR - http://www.scopus.com/inward/record.url?scp=71549165765&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=71549165765&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2009.10.013
DO - 10.1016/j.devcel.2009.10.013
M3 - Article
C2 - 19922871
AN - SCOPUS:71549165765
SN - 1534-5807
VL - 17
SP - 662
EP - 673
JO - Developmental cell
JF - Developmental cell
IS - 5
ER -