Exon junction complex-associated multi-adapter RNPS1 nucleates splicing regulatory complexes to maintain transcriptome surveillance
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 interact...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
30 May 2022
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| In: |
Nucleic acids research
Year: 2022, Volume: 50, Issue: 10, Pages: 5899-5918 |
| ISSN: | 1362-4962 |
| DOI: | 10.1093/nar/gkac428 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1093/nar/gkac428 Verlag, kostenfrei, Volltext: https://academic.oup.com/nar/article/50/10/5899/6595294 
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| Author Notes: | Lena P. Schlautmann, Jan-Wilm Lackmann, Janine Altmüller, Christoph Dieterich, Volker Boehm and Niels H. Gehring |
| Summary: | 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. |
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| Item Description: | Gesehen am 25.09.2024 |
| Physical Description: | Online Resource |
| ISSN: | 1362-4962 |
| DOI: | 10.1093/nar/gkac428 |