Exon junction complex-associated multi-adapter RNPS1 nucleates splicing regulatory complexes to maintain transcriptome surveillance

Schlautmann, L.P.; Lackmann, J.W.; Altmüller, J.; Dieterich, C.; Boehm, V.; Gehring, N.H.

Exon junction complex-associated multi-adapter RNPS1 nucleates splicing regulatory complexes to maintain transcriptome surveillance

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Item Type:	Article
Title:	Exon junction complex-associated multi-adapter RNPS1 nucleates splicing regulatory complexes to maintain transcriptome surveillance
Creators:	Schlautmann, L.P. ORCID: https://orcid.org/0000-0001-7439-7723, Lackmann, J.W. ORCID: https://orcid.org/0000-0001-8182-8034, Altmüller, J. ORCID: https://orcid.org/0000-0003-4372-1521, Dieterich, C. ORCID: https://orcid.org/0000-0001-9468-6311, Boehm, V. ORCID: https://orcid.org/0000-0001-7588-9842 and Gehring, N.H. ORCID: https://orcid.org/0000-0001-7792-1164
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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