LncRNA SMARCD3-OT1 Promotes Muscle Hypertrophy and Fast-Twitch Fiber Transformation via Enhancing SMARCD3X4 Expression

Abstract

Long noncoding RNA (lncRNA) plays a crucial part in all kinds of life activities, especially in myogenesis. SMARCD3 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily d, member 3) is a member of the SWI/SNF protein complex and was reported to be required for cell proliferation and myoblast differentiation. In this study, we identified a new lncRNA named SMARCD3-OT1 (SMARCD3 overlapping lncRNA), which strongly regulated the development of myogenesis by improving the expression of SMARCD3X4 (SMARCD3 transcripts 4). We overexpressed and knockdown the expression of SMARCD3-OT1 and SMARCD3X4 to investigate their function on myoblast proliferation and differentiation. Cell experiments proved that SMARCD3-OT1 and SMARCD3X4 promoted myoblast proliferation through the CDKN1A pathway and improved differentiation of differentiated myoblasts through the MYOD pathway. Moreover, they upregulated the fast-twitch fiber-related genes and downregulated the slow-twitch fiber-related genes, which indicated that they facilitated the slow-twitch fiber to transform into the fast-twitch fiber. The animals’ experiments supported the results above, demonstrating that SMARCD3-OT1 could induce muscle hypertrophy and fast-twitch fiber transformation. In conclusion, SMARCD3-OT1 can improve the expression of SMARCD3X4, thus inducing muscle hypertrophy. In addition, SMARCD3-OT1 can facilitate slow-twitch fibers to transform into fast-twitch fibers.

Exploring the association between fat-related traits in chickens and the RGS16 gene: insights from polymorphism and functional validation analysis

“…RT-qPCR was performed using a ChamQ Universal SYBR qPCR Master Mix (Vazyme, Nanjing, China) in a Bio-Rad CFX96 Real-Time Detection System. Data were analyzed using the 2 −△△Ct method with chicken GAPDH as the reference gene (16). The RT-qPCR primers were designed in Primer-BLAST 1 and their detail were listed in Supplementary Table 1.…”

The Functional Role of Long Non-Coding RNA in Myogenesis and Skeletal Muscle Atrophy

“…In chickens, lncRNA SMRCD3-OT1 , which is partly overlaid on the Smarcd3x4 gene, was highly enriched in the breast and leg muscles [ 131 ]. SMARCD3-OT1 expression remained constant in chicken primary myoblasts in a proliferative state but increased after the induction of myogenic differentiation.…”

“…Moreover, SMARCD3-OT1 induced hypertrophy and a fast-twitch muscle fiber phenotype in chicken skeletal muscles ( Table 1 ). Thus, SMARCD3-OT1 promotes cell proliferation and myotube formation, and can also induce fast-twitch muscle fiber-related genes in chicken primary myoblasts by increasing Smarcd3x4 expression ( Figure 1 , left panel) [ 131 ]. Smarcd3x4 is one of the isoforms of the evolutionarily conserved Smarcd3 gene [ 131 ], which encodes a component of the SWI/SNF complex.…”

“…Thus, SMARCD3-OT1 promotes cell proliferation and myotube formation, and can also induce fast-twitch muscle fiber-related genes in chicken primary myoblasts by increasing Smarcd3x4 expression ( Figure 1 , left panel) [ 131 ]. Smarcd3x4 is one of the isoforms of the evolutionarily conserved Smarcd3 gene [ 131 ], which encodes a component of the SWI/SNF complex. Therefore, investigating whether SMARCD3-OT1 and its molecular function are also evolutionarily conserved in humans is important.…”

LncEDCH1 g.1703613 T>C regulates chicken carcass traits by targeting miR-196-2-3p

“…LncEDCH1 promotes muscle atrophy reduction by interacting with SERCA2 and improving mitochondrial function ( Cai et al, 2022a ). LncRNA SMARCD3-OT1 drives muscle hypertrophy and facilitates the transition to fast-twitch fiber type by enhancing SMARCD3×4 expression ( Zhang et al, 2022 ).…”