Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 293, Issue 1, Pages C451-C457Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00077.2007
Keywords
muscular dystrophy; posttranscriptional; gene regulation
Categories
Funding
- NEI NIH HHS [EY12998] Funding Source: Medline
- NIAMS NIH HHS [AR45617] Funding Source: Medline
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MicroRNAs are highly conserved, noncoding RNAs involved in posttranscriptional gene silencing. MicroRNAs have been shown to be involved in a range of biological processes, including myogenesis and muscle regeneration. The objective of this study was to test the hypothesis that microRNA expression is altered in dystrophic muscle, with the greatest change occurring, of the muscles examined, in the diaphragm. The expression of the muscle-enriched microRNAs was determined in the soleus, plantaris, and diaphragm muscles of control and dystrophin-deficient (mdx) mice by semiquantitative PCR. In the soleus and plantaris, expression of the mature microRNA 133a (miR133a) and miR-206, respectively, was decreased by similar to 25%, whereas in the diaphragm, miR-206 expression increased by 4.5-fold relative to control. The increased expression of miR-206 in the mdx diaphragm was paralleled by a 4.4-fold increase in primary miRNA-206 (pri-miRNA-206) transcript level. Expression of Myod1 was elevated 2.7-fold only in the mdx diaphragm, consistent with an earlier finding demonstrating Myod1 can activate pri-miRNA-206 transcription. Transcript levels of Drosha and Dicer, major components of microRNA biogenesis pathway, were unchanged in mdx muscle, suggesting the pathway is not altered under dystrophic conditions. Previous in vitro analysis found miR-206 was capable of repressing utrophin expression; however, under dystrophic conditions, both utrophin transcript and protein levels were significantly increased by 69% and 3.9-fold, respectively, a finding inconsistent with microRNA regulation. These results are the first to report alterations in expression of muscle-enriched microRNAs in skeletal muscle of the mdx mouse, suggesting microRNAs may have a role in the pathophysiology of muscular dystrophy.
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