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Thyroid hormone regulates muscle fiber type conversion via miR-133a1
- Source :
- The Journal of Cell Biology
- Publication Year :
- 2014
- Publisher :
- The Rockefeller University Press, 2014.
-
Abstract
- Thyroid hormone promotes slow-to-fast muscle fiber type conversion by inducing miR-133a1 and thereby repressing the expression of the slow muscle determinant TEAD1.<br />It is known that thyroid hormone (TH) is a major determinant of muscle fiber composition, but the molecular mechanism by which it does so remains unclear. Here, we demonstrated that miR-133a1 is a direct target gene of TH in muscle. Intriguingly, miR-133a, which is enriched in fast-twitch muscle, regulates slow-to-fast muscle fiber type conversion by targeting TEA domain family member 1 (TEAD1), a key regulator of slow muscle gene expression. Inhibition of miR-133a in vivo abrogated TH action on muscle fiber type conversion. Moreover, TEAD1 overexpression antagonized the effect of miR-133a as well as TH on muscle fiber type switch. Additionally, we demonstrate that TH negatively regulates the transcription of myosin heavy chain I indirectly via miR-133a/TEAD1. Collectively, we propose that TH inhibits the slow muscle phenotype through a novel epigenetic mechanism involving repression of TEAD1 expression via targeting by miR-133a1. This identification of a TH-regulated microRNA therefore sheds new light on how TH achieves its diverse biological activities.
- Subjects :
- Biology
Article
Cell Line
Mice
RNA interference
Myosin
Gene expression
medicine
Animals
Enhancer
Promoter Regions, Genetic
Psychological repression
TEAD1
Transcription factor
Research Articles
Mice, Knockout
Binding Sites
Base Sequence
Myosin Heavy Chains
Skeletal muscle
TEA Domain Transcription Factors
Cell Biology
Molecular biology
Cell biology
Rats
DNA-Binding Proteins
Mice, Inbred C57BL
MicroRNAs
medicine.anatomical_structure
Muscle Fibers, Fast-Twitch
Triiodothyronine
RNA Interference
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 15408140 and 00219525
- Volume :
- 207
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- The Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....e170f2f69a548c332b579865ae1eaffb