LncRNA OIP5-AS1-directed miR-7 degradation promotes MYMX production during human myogenesis

• Published in: Nucleic acids research 2022-07, Vol.50 (12), p.7115-7133
• Main Authors: Yang, Jen-Hao, Chang, Ming-Wen, Tsitsipatis, Dimitrios, Yang, Xiaoling, Martindale, Jennifer L, Munk, Rachel, Cheng, Aiwu, Izydore, Elizabeth, Pandey, Poonam R, Piao, Yulan, Mazan-Mamczarz, Krystyna, De, Supriyo, Abdelmohsen, Kotb, Gorospe, Myriam
• Format: Article
• Language: English
• Subjects: Humans; MicroRNAs - genetics; Muscle Development - genetics; RNA and RNA-protein complexes; RNA, Long Noncoding - genetics
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkac524

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.