LncRNA OIP5-AS1-directed miR-7 degradation promotes MYMX production during human myogenesis |
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| Authors: | Jen-Hao Yang,Ming-Wen Chang,Dimitrios Tsitsipatis,Xiaoling Yang,Jennifer L Martindale,Rachel Munk,Aiwu Cheng,Elizabeth Izydore,Poonam R Pandey,Yulan Piao,Krystyna Mazan-Mamczarz,Supriyo De,Kotb Abdelmohsen,Myriam Gorospe |
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| Affiliation: | Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Blvd, Baltimore, MD 21224, USA |
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| 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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