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

• Verfasst von: Schlautmann, Lena P. [VerfasserIn]
• Verfasst von: Lackmann, Jan-Wilm [VerfasserIn]
• Verfasst von: Altmüller, Janine [VerfasserIn]
• Verfasst von: Dieterich, Christoph [VerfasserIn]
• Verfasst von: Böhm, Volker [VerfasserIn]
• Verfasst von: Gehring, Niels H. [VerfasserIn]
• Titel: Exon junction complex-associated multi-adapter RNPS1 nucleates splicing regulatory complexes to maintain transcriptome surveillance
• Verf.angabe: Lena P. Schlautmann, Jan-Wilm Lackmann, Janine Altmüller, Christoph Dieterich, Volker Boehm and Niels H. Gehring
• E-Jahr: 2022
• Jahr: 30 May 2022
• Umfang: 20 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 25.09.2024
• Titel Quelle: Enthalten in: Nucleic acids research
• Ort Quelle: Oxford : Oxford Univ. Press, 1974
• Jahr Quelle: 2022
• Band/Heft Quelle: 50(2022), 10, Seite 5899-5918
• ISSN Quelle: 1362-4962
• DOI: doi:10.1093/nar/gkac428
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1903448867

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.