Abstract:
RNA-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.
摘要:
具有富含丝氨酸结构域1(RNPS1)的RNA结合蛋白在剪接过程中沉积在mRNA上,并伴随与外显子连接复合物(EJC)结合。RNPS1参与转录后基因调控,包括本构拼接和交替拼接,转录调控和无义介导的mRNA衰减。在这项研究中,我们发现RNPS1或其分离的富含丝氨酸的结构域(S结构域)的连接导致HIV-1剪接底物的外显子包含。相比之下,过表达RNPS1的RRM结构域以显性负方式起作用,并导致内源性凋亡前mRNA(Bcl-X和MCL-1)的外显子跳跃。Further,核心EJC蛋白的连接,eIF4A3,MAGOH,或Y14,不会导致HIV底物的外显子包含。一起,我们的结果证明了RNPS1及其结构域是如何差异参与可变剪接活性的.