AI Article Synopsis
- Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play crucial roles in regulating gene expression during muscle development and regeneration.
- The study focuses on lncRNA OIP5-AS1, which increases while miR-7 levels decrease during early human myogenesis, facilitating myoblast fusion into myotubes.
- OIP5-AS1 promotes the decay of miR-7, leading to the derepression of the target MYMX mRNA, ultimately enhancing myotube formation by increasing the production of the fusogenic protein myomixer (MYMX).
Article Abstract
Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) modulate gene expression programs in physiology and disease. Here, we report a noncoding RNA regulatory network that modulates myoblast fusion into multinucleated myotubes, a process that occurs during muscle development and muscle regeneration after injury. In early stages of human myogenesis, the levels of lncRNA OIP5-AS1 increased, while the levels of miR-7 decreased. Moreover, OIP5-AS1 bound and induced miR-7 decay via target RNA-directed miRNA decay; accordingly, loss of OIP5-AS1 attenuated, while antagonizing miR-7 accelerated, myotube formation. We found that the OIP5-AS1-mediated miR-7 degradation promoted myoblast fusion, as it derepressed the miR-7 target MYMX mRNA, which encodes the fusogenic protein myomixer (MYMX). Remarkably, an oligonucleotide site blocker interfered with the OIP5-AS1-directed miR-7 degradation, allowing miR-7 to accumulate, lowering MYMX production and suppressing myotube formation. These results highlight a mechanism whereby lncRNA OIP5-AS1-mediated miR-7 decay promotes myotube formation by stimulating a myogenic fusion program.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262585 | PMC |
| http://dx.doi.org/10.1093/nar/gkac524 | DOI Listing |
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