1. mRNA m 5 C inhibits adipogenesis and promotes myogenesis by respectively facilitating YBX2 and SMO mRNA export in ALYREF-m 5 C manner.
- Author
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Liu Y, Yang Y, Wu R, Gao CC, Liao X, Han X, Zeng B, Huang C, Luo Y, Liu Y, Chen Y, Chen W, Liu J, Jiang Q, Zhao Y, Bi Z, Guo G, Yao Y, Xiang Y, Zhang X, Valencak TG, Wang Y, and Wang X
- Subjects
- Animals, Muscle Development genetics, RNA Transport, RNA, Messenger genetics, RNA, Messenger metabolism, Swine, Adipogenesis genetics, RNA-Binding Proteins metabolism
- Abstract
Although 5-methylcytosine (m
5 C) has been identified as a novel and abundant mRNA modification and associated with energy metabolism, its regulation function in adipose tissue and skeletal muscle is still limited. This study aimed at investigating the effect of mRNA m5 C on adipogenesis and myogenesis using Jinhua pigs (J), Yorkshire pigs (Y) and their hybrids Yorkshire-Jinhua pigs (YJ). We found that Y grow faster than J and YJ, while fatness-related characteristics observed in Y were lower than those of J and YJ. Besides, total mRNA m5 C levels and expression rates of NSUN2 were higher both in backfat layer (BL) and longissimus dorsi muscle (LDM) of Y compared to J and YJ, suggesting that higher mRNA m5 C levels positively correlate with lower fat and higher muscle mass. RNA bisulfite sequencing profiling of m5 C revealed tissue-specific and dynamic features in pigs. Functionally, hyper-methylated m5 C-containing genes were enriched in pathways linked to impaired adipogenesis and enhanced myogenesis. In in vitro, m5 C inhibited lipid accumulation and promoted myogenic differentiation. Furthermore, YBX2 and SMO were identified as m5 C targets. Mechanistically, YBX2 and SMO mRNAs with m5 C modification were recognized and exported into the cytoplasm from the nucleus by ALYREF, thus leading to increased YBX2 and SMO protein expression and thereby inhibiting adipogenesis and promoting myogenesis, respectively. Our work uncovered the critical role of mRNA m5 C in regulating adipogenesis and myogenesis via ALYREF-m5 C-YBX2 and ALYREF-m5 C-SMO manners, providing a potential therapeutic target in the prevention and treatment of obesity, skeletal muscle dysfunction and metabolic disorder diseases., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)- Published
- 2022
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