Multi-posttranscriptional regulations lessen the repressive effect of SRPK1 on brown adipogenesis

作者：Lin Jung Chun^*

来源：Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids, 2018, 1863(5): 503-514.

DOI：10.1016/j.bbalip.2018.02.004

• Alternative splicing
• Brown adipocyte
• miR-485
• RBM4
• SRPK1

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.

• 出版日期2018-5