As a fundamental mechanism of post-transcriptional epigenetic regulation, RNA modifications have attracted increasing research interest in recent years. N6-methyladenosine (m6A), the most abundant internal RNA modification, plays a crucial role in regulating multiple stages of mRNA metabolism including processing, transport, translation, and degradation. The differentiation of bovine preadipocytes into mature adipocytes is regulated at multiple levels including transcriptional, post-transcription, translation, and post-translation levels. However, the precise regulatory mechanism of m6A modification during bovine adipogenesis remains poorly understood. In this study, we conducted MeRIP-seq and RNA-seq analyses across three stages of bovine preadipocyte differentiation—pre-differentiation (day 0, D0), early differentiation (day 2, D2), and late differentiation (day 8, D8)—to characterize the dynamic landscape of m⁶A methylation during adipogenesis. The analysis identified 400 genes exhibiting significant changes in both m⁶A modification levels and mRNA expression during the differentiation phase (D0–D2), while 592 genes exhibited such changes during the lipid accumulation phase (D2–D8). These results indicate that m⁶A modification likely contributes to adipogenesis by modulating the expression of these genes. To further investigate the functional relevance of the m⁶A machinery, we knocked down the m⁶A writer METTL14, a core component of the methyltransferase complex, and performed RNA-seq analysis. Integrative analysis of the differentially expressed genes (DEGs) with the stage-specific expression profile revealed a set of candidate genes potentially regulated by METTL14 that participate in early preadipocyte differentiation and late-stage lipid accumulation. These findings provide new evidence for the molecular mechanisms underlying m⁶A modification during bovine adipogenesis and highlight a functional contribution of the m⁶A writer METTL14.
Zhang et al. (Mon,) studied this question.