LncRSFD Alternative Splicing Modulates the Proliferation and Differentiation of Adipocytes Through Sponging miRNAs

Adipose deposition critically determines meat quality and metabolic health in livestock, yet its molecular regulation needs further investigation. Recently, long noncoding RNA (lncRNA) alternative splicing events have been found to play a role in adipose tissue accumulation and are abundant in animals. Nonetheless, lncRNA alternative splicing, an underexplored regulatory layer in adipogenesis, may drive functional diversification in fat metabolism. Here, we investigate the functional divergence of two splicing isoforms (lncRSFD‐L and lncRSFD‐S) derived from the lncRNA related to sheep fatty deposits (lncRSFD). Through gain‐of‐function experiments in adipocytes, we demonstrate that lncRSFD‐L/S can significantly promote the proliferation, differentiation, and lipid metabolism of adipocytes. Mechanistically, lncRSFD‐L directly targets three miRNAs (let‐7b, miR‐3959‐3p, and miR‐323a‐5p), while lncRSFD‐S specifically binds to let‐7b and miR‐323a‐5p. It is worth noting that these miRNAs display dual regulatory effects: they suppress proliferation and viability of adipocytes but simultaneously promote differentiation and lipid metabolism. This research advances our understanding of alternative splicing mechanisms, and provides valuable insights for molecular breeding strategies.