Apoptotic chromatin condensation inducer in the nucleus (also referred as Acin1) was first characterized as an RNA-binding protein involved in apoptosis. In later reports, Acin1 was identified as an auxiliary component of the exon junction complex (EJC) which is assembled throughout pre-messenger RNA splicing. In this study, results of whole-transcriptome analyses revealed reduced expressions and reprogrammed splicing profiles of Acin1 transcripts throughout development of brown adipose tissues (BATs) that execute non-shivering thermogenesis in small rodents and infants by consuming lipids. Depletion of endogenous Acin1 isoforms led to activation of brown adipogenic signatures in mouse C3H10T1/2 fibroblasts. Nevertheless, overexpressions of the Acin1-L or Acin1-S isoform exerted discriminative influences on brown adipogenesis and reprogramming of the expression of serine/arginine-rich splicing factor 3 (SRSF3) through an alternative splicing-coupled nonsense-mediated decay mechanism in a sequence-specific manner. Moreover, the Acin1-SRSF3 axis constitutes a regulatory pathway that participates in the brown adipocyte-related splicing network. Taken together, the interplay between accessory EJC components and splicing regulators constitutes an emerging mechanism for differentially manipulating the activity of brown adipogenesis via alternative splicing network.
|期刊||Biochimica et Biophysica Acta - Gene Regulatory Mechanisms|
|出版狀態||已發佈 - 九月 2020|
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology