The effect of lnc-ORA knockout on muscle fiber type transformation in mouse leg muscle.

Skeletal muscle fiber type conversion is usually regulated by coding and non-coding RNA, which is closely related to obesity, Duchenne muscular dystrophy and sarcopenia. Furthermore, lnc-ORA KO mice were first constructed, and the results showed that lnc-ORA deficiency significantly increased exercise endurance, oxidative myofibers and mitochondrial function. Meanwhile, combining transcriptomic and proteomic data showed that lnc-ORA deficiency improved the biological processes and pathways related to the transformation of skeletal muscle fiber types. Mechanically, MYH7 is a target of lnc-ORA by multi-omics and RNA pull-down data, and it was degraded by interacting with ARIH1 through ubiquitination pathway. Importantly, lnc-ORA overexpression decreased the expression of MYH7 and enhanced the interaction of MYH7 and ARIH1, while lnc-ORA knockdown was the opposite. Overall, integrating transcriptomic and proteomic reveals the positive role of lnc-ORA deficiency on slow myofiber type formation via upregulating the level of MYH7 and inhibiting interaction between MYH7 and ARIH1. Our findings provide novel insights into the regulation of lncRNA on skeletal muscle fiber types. Overall design: To investigate the role of lnc-ORA in skeletal muscle fiber type transformation, We generated lnc-ORA knockout (KO) mice using the CRISPR genome-editing system with the C57BL/6 background.Subsequently, we performed RNA-seq on the gastrocnemius muscle of 15-week-old lnc-ORA knockout mice and conducted gene expression analysis.