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Item Type: | Article | ||||
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Title: | Exon junction complex-associated multi-adapter RNPS1 nucleates splicing regulatory complexes to maintain transcriptome surveillance | ||||
Creators Name: | Schlautmann, L.P. and Lackmann, J.W. and Altmüller, J. and Dieterich, C. and Boehm, V. and Gehring, N.H. | ||||
Abstract: | The exon junction complex (EJC) is an RNA-binding multi-protein complex with critical functions in post-transcriptional gene regulation. It is deposited on the mRNA during splicing and regulates diverse processes including pre-mRNA splicing and nonsense-mediated mRNA decay (NMD) via various interacting proteins. The peripheral EJC-binding protein RNPS1 was reported to serve two insufficiently characterized functions: suppressing mis-splicing of cryptic splice sites and activating NMD in the cytoplasm. The analysis of transcriptome-wide effects of EJC and RNPS1 knockdowns in different human cell lines supports the conclusion that RNPS1 can moderately influence NMD activity, but is not a globally essential NMD factor. However, numerous aberrant splicing events strongly suggest that the main function of RNPS1 is splicing regulation. Rescue analyses revealed that the RRM and C-terminal domain of RNPS1 both contribute partially to regulate RNPS1-dependent splicing events. We defined the RNPS1 core interactome using complementary immunoprecipitations and proximity labeling, which identified interactions with splicing-regulatory factors that are dependent on the C-terminus or the RRM domain of RNPS1. Thus, RNPS1 emerges as a multifunctional splicing regulator that promotes correct and efficient splicing of different vulnerable splicing events via the formation of diverse splicing-promoting complexes. | ||||
Keywords: | Exons, RNA Splicing, RNA-Binding Proteins, Ribonucleoproteins, Transcriptome | ||||
Source: | Nucleic Acids Research | ||||
ISSN: | 0305-1048 | ||||
Publisher: | Oxford University Press | ||||
Volume: | 50 | ||||
Number: | 10 | ||||
Page Range: | 5899-5918 | ||||
Date: | 10 June 2022 | ||||
Official Publication: | https://doi.org/10.1093/nar/gkac428 | ||||
PubMed: | View item in PubMed | ||||
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