Serine‐rich domain of RNPS1 functions in activation of alternative splicing

Abstract

AbstractRNA‐binding protein with serine‐rich domain 1 (RNPS1) gets deposited on the mRNA during the process of splicing and concomitantly associates with the exon junction complex (EJC). RNPS1 participates in post‐transcriptional gene regulation, including constitutive and alternative splicing, transcriptional regulation and nonsense‐mediated mRNA decay. In this study, we found that the tethering of RNPS1 or its isolated serine‐rich domain (S domain) causes exon inclusion of an HIV‐1 splicing substrate. In contrast, overexpressing the RRM domain of RNPS1 acts in a dominant negative manner and leads to the exon skipping of endogenous apoptotic pre‐mRNAs (Bcl‐X and MCL‐1). Further, tethering of core EJC proteins, eIF4A3, MAGOH, or Y14, does not lead to exon inclusion of an HIV substrate. Together, our results demonstrate how RNPS1 and its domains are differentially involved in alternative splicing activity.