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RNA-binding protein AUF1 promotes myogenesis by regulating MEF2C expression levels
Amaresh C Panda1, Kotb Abdelmohsen1, Je-Hyun Yoon1
1Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
Molecular and Cellular Biology
|June 4, 2014
Summary
The RNA-binding protein AUF1 (AU-binding factor 1) promotes skeletal muscle differentiation by enhancing MEF2C translation and transcription. Lowering AUF1 impairs myogenesis, highlighting AUF1
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- AUF1 (AU-binding factor 1), also known as hnRNP D, is an RNA-binding protein regulating mRNA fate.
- AUF1 targets mRNAs encoding muscle-specific factors, suggesting a role in skeletal muscle differentiation.
Purpose of the Study:
- To investigate the function of AUF1 in skeletal muscle differentiation.
- To determine AUF1's specific targets and mechanisms in myogenesis.
Main Methods:
- RNP immunoprecipitation (RIP) analysis to identify AUF1-bound mRNAs.
- mRNA half-life measurements and polysome distribution analysis.
- Investigating AUF1's role in transcriptional regulation.
Main Results:
- AUF1 binds to Mef2c mRNA in C2C12 myocytes during differentiation.
- AUF1 promotes MEF2C translation by associating with the Mef2c 3' UTR, without affecting mRNA stability.
- AUF1 also enhances Mef2c gene transcription.
- Reduced AUF1 levels delay myogenesis, and MEF2C restoration partially rescues this defect.
Conclusions:
- AUF1 plays a crucial role in promoting skeletal muscle differentiation.
- MEF2C is identified as a key effector of the myogenesis program regulated by AUF1.
- AUF1 influences myogenesis through both posttranscriptional and transcriptional mechanisms involving MEF2C.
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