LncRNA OIP5-AS1-directed miR-7 degradation promotes MYMX production during human myogenesis. Issue 12 (23rd June 2022)

• Record Type: Journal Article
• 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
• Is Part Of: Nucleic acids research. Volume 50:Issue 12(2022)
• Page Start: 7115
• Page End: 7133
• Publication Date: 2022-06-23
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkac524
• Languages: English
• ISSNs: 0305-1048

Abstract

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.