Alternative splicing has been widely demonstrated to function as pivotal regulation in specifying cellular fates and biological functions. The relative expression or cellular localization of a splicing factor constitutes an important mechanism in spatiotemporal programming of cell- and stage-specific splicing profiles. In this study, results of deep RNA-sequencing (RNA-Seq) analyses first revealed the reprogrammed splicing profile and reduced expression of serine/arginine-rich splicing factor protein kinase 1 (SRPK1) throughout the development of brown adipose tissue (BAT). A gradual increase in the exon 10-skipped SRPK1 transcript, a potential target of a nonsense-mediated decay (NMD) mechanism, was noted during brown adipogenesis. Elevated RBM4a constituted the regulatory mechanism that led to skipping of SRPK1 exon 10. Moreover, brown adipogenesis-induced upregulation of microRNA (miR)-485 interfered with SRPK1 expression by targeting its 3'-untranslated region (UTR). Depletion of endogenous SRPK1 enhanced the development of C3H10T1/2 cells toward brown adipocytes. Taking our results together, multiple post-transcriptional regulations reduced SRPK1 expression, which subsequently affected brown adipogenesis.
Keywords: Alternative splicing; Brown adipocyte; RBM4; SRPK1; miR-485.
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