Universität zu Köln

Schlautmann, Lena P., Lackmann, Jan-Wilm ORCID: 0000-0001-8182-8034, Altmueller, Janine, Dieterich, Christoph ORCID: 0000-0001-9468-6311, Boehm, Volker ORCID: 0000-0001-7588-9842 and Gehring, Niels H. (2022). Exon junction complex-associated multi-adapter RNPS1 nucleates splicing regulatory complexes to maintain transcriptome surveillance. Nucleic Acids Res., 50 (10). S. 5899 - 5919. OXFORD: OXFORD UNIV PRESS. ISSN 1362-4962

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schlautmann, Lena P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lackmann, Jan-Wilm UNSPECIFIED orcid.org/0000-0001-8182-8034 UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Dieterich, Christoph UNSPECIFIED orcid.org/0000-0001-9468-6311 UNSPECIFIED Boehm, Volker UNSPECIFIED orcid.org/0000-0001-7588-9842 UNSPECIFIED Gehring, Niels H. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-689230
DOI:	10.1093/nar/gkac428
Journal or Publication Title:	Nucleic Acids Res.
Volume:	50
Number:	10
Page Range:	S. 5899 - 5919
Date:	2022
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1362-4962
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NONSENSE-MEDIATED DECAY; FREE QUANTIFICATION; PROTEIN COMPLEX; SR PROTEIN; RNA DECAY; IDENTIFICATION; REVEALS; NMD; COMMUNICATION; DEFINITION Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68923