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RNA-binding proteins direct myogenic cell fate decisions
Joshua R Wheeler1,2,3,4,5, Oscar N Whitney6, Thomas O Vogler2,7,8
1Department of Biochemistry, University of Colorado, Boulder, United States.
Elife
|June 13, 2022
Summary
RNA-binding proteins (RBPs) are crucial for muscle repair. Temporally regulated RBP expression, like Hnrnpa2b1, guides muscle stem cell fate during regeneration and differentiation.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- RNA-binding proteins (RBPs) are vital for skeletal muscle regeneration.
- Mutations in RBPs can lead to muscle degeneration and neuromuscular diseases.
- The precise roles of RBPs in directing cell fate during muscle regeneration are not fully understood.
Purpose of the Study:
- To investigate the temporal regulation of RBP expression during skeletal muscle regeneration.
- To identify specific RBPs that regulate myogenic cell fate decisions.
- To elucidate the function of the neuromuscular disease-associated RBP Hnrnpa2b1 in myogenesis.
Main Methods:
- Single-cell RNA-sequencing of regenerating mouse skeletal muscle.
- Machine learning algorithms for RBP engagement scoring.
- Analysis of RBP expression dynamics during myogenic differentiation.
Main Results:
- RBP expression, including disease-associated RBPs, is temporally regulated in muscle stem cells during regeneration.
- Hnrnpa2b1 acts as a key regulator specifying differentiation during myogenesis.
- The timing of RBP expression influences post-transcriptional regulation of mRNAs, controlling cell fate.
Conclusions:
- Temporal RBP expression patterns are critical for coordinating cell fate decisions in skeletal muscle stem cells.
- Hnrnpa2b1 plays a significant role in controlling myogenic cell fate transitions.
- Understanding RBP regulation offers insights into neuromuscular disease mechanisms and muscle regeneration.
Keywords:
RNA splicingRNA-binding proteinmousepost-transcriptional regulationregenerationregenerative medicineskeletal musclesplicing networkstem cellsMore Related Videos
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