COPS3 AS lncRNA enhances myogenic differentiation and maintains fast-type myotube phenotype

Abstract

Long non-coding RNAs (lncRNAs) play essential roles in myogenesis. Here, we identified a novel long non-coding RNA, named COPS3 AS lncRNA (COP9 signalosome complex subunit 3 antisense lncRNA), which was transcribed from the mouse COPS3 gene antisense strand and highly expressed in glycolytic muscle fibers. Functionally, COPS3 AS lncRNA knockdown inhibited myogenic differentiation in myoblasts, whereas its overexpression promoted the process. Moreover, COPS3 AS lncRNA maintained the fast-twitch myotubes phenotype. Mechanistically, although COPS3 AS lncRNA did not form AS lncRNA/mRNA dimer with COPS3 mRNA, it as a competing endogenous RNA (ceRNA) to sponge miR-762, promoted myogenic differentiation and Fast-MyHC expression by modulating miR-762 target gene myogenic differentiation 1 (MyoD1). Taken together, COPS3 AS lncRNA is a key candidate regulator of myogenesis and fast-MyHC myotubes specification by miR-762/MyoD signalling axis.

Keywords: COPS3 AS lncRNA; MyoD; Myogenesis; Myotube phenotype; miR-762.