Abstract
MicroRNAs modulate cellular phenotypes by inhibiting expression of mRNA targets. In this study, we have shown that the muscle-specific microRNAs miR-133a-1 and miR-133a-2 are essential for multiple facets of skeletal muscle function and homeostasis in mice. Mice with genetic deletions of miR-133a-1 and miR-133a-2 developed adult-onset centronuclear myopathy in type II (fast-twitch) myofibers, accompanied by impaired mitochondrial function, fast-to-slow myofiber conversion, and disarray of muscle triads (sites of excitation-contraction coupling). These abnormalities mimicked human centronuclear myopathies and could be ascribed, at least in part, to dysregulation of the miR-133a target mRNA that encodes dynamin 2, a GTPase implicated in human centronuclear myopathy. Our findings reveal an essential role for miR-133a in the maintenance of adult skeletal muscle structure, function, bioenergetics, and myofiber identity; they also identify a potential modulator of centronuclear myopathies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3258-3268 |
| Number of pages | 11 |
| Journal | Journal of Clinical Investigation |
| Volume | 121 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2011 |
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ASJC Scopus subject areas
- Medicine(all)
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Mice lacking microRNA 133a develop dynamin 2-dependent centronuclear myopathy. / Liu, Ning; Bezprozvannaya, Svetlana; Shelton, John M.; Frisard, Madlyn I.; Hulver, Matthew W.; McMillan, Ryan P.; Wu, Yaru; Voelker, Kevin A.; Grange, Robert W.; Richardson, James A.; Bassel-Duby, Rhonda; Olson, Eric N.
In: Journal of Clinical Investigation, Vol. 121, No. 8, 01.08.2011, p. 3258-3268.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mice lacking microRNA 133a develop dynamin 2-dependent centronuclear myopathy
AU - Liu, Ning
AU - Bezprozvannaya, Svetlana
AU - Shelton, John M.
AU - Frisard, Madlyn I.
AU - Hulver, Matthew W.
AU - McMillan, Ryan P.
AU - Wu, Yaru
AU - Voelker, Kevin A.
AU - Grange, Robert W.
AU - Richardson, James A.
AU - Bassel-Duby, Rhonda
AU - Olson, Eric N.
PY - 2011/8/1
Y1 - 2011/8/1
N2 - MicroRNAs modulate cellular phenotypes by inhibiting expression of mRNA targets. In this study, we have shown that the muscle-specific microRNAs miR-133a-1 and miR-133a-2 are essential for multiple facets of skeletal muscle function and homeostasis in mice. Mice with genetic deletions of miR-133a-1 and miR-133a-2 developed adult-onset centronuclear myopathy in type II (fast-twitch) myofibers, accompanied by impaired mitochondrial function, fast-to-slow myofiber conversion, and disarray of muscle triads (sites of excitation-contraction coupling). These abnormalities mimicked human centronuclear myopathies and could be ascribed, at least in part, to dysregulation of the miR-133a target mRNA that encodes dynamin 2, a GTPase implicated in human centronuclear myopathy. Our findings reveal an essential role for miR-133a in the maintenance of adult skeletal muscle structure, function, bioenergetics, and myofiber identity; they also identify a potential modulator of centronuclear myopathies.
AB - MicroRNAs modulate cellular phenotypes by inhibiting expression of mRNA targets. In this study, we have shown that the muscle-specific microRNAs miR-133a-1 and miR-133a-2 are essential for multiple facets of skeletal muscle function and homeostasis in mice. Mice with genetic deletions of miR-133a-1 and miR-133a-2 developed adult-onset centronuclear myopathy in type II (fast-twitch) myofibers, accompanied by impaired mitochondrial function, fast-to-slow myofiber conversion, and disarray of muscle triads (sites of excitation-contraction coupling). These abnormalities mimicked human centronuclear myopathies and could be ascribed, at least in part, to dysregulation of the miR-133a target mRNA that encodes dynamin 2, a GTPase implicated in human centronuclear myopathy. Our findings reveal an essential role for miR-133a in the maintenance of adult skeletal muscle structure, function, bioenergetics, and myofiber identity; they also identify a potential modulator of centronuclear myopathies.
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U2 - 10.1172/JCI46267
DO - 10.1172/JCI46267
M3 - Article
VL - 121
SP - 3258
EP - 3268
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 8
ER -