PT  - JOURNAL ARTICLE
AU  - Lena P. Schlautmann
AU  - Volker Boehm
AU  - Jan-Wilm Lackmann
AU  - Janine Altmüller
AU  - Christoph Dieterich
AU  - Niels H. Gehring
TI  - Exon junction complex-associated multi-adapter RNPS1 nucleates splicing regulatory complexes to maintain transcriptome surveillance
AID  - 10.1101/2021.08.20.457088
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.20.457088
4099  - http://biorxiv.org/content/early/2021/08/20/2021.08.20.457088.short
4100  - http://biorxiv.org/content/early/2021/08/20/2021.08.20.457088.full
AB  - 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, mRNA export, mRNA translation, and nonsense-mediated mRNA decay (NMD) via various interacting peripheral proteins. The EJC-binding protein RNPS1 might serve two functions: it suppresses mis-splicing of cryptic splice sites and activates NMD in the cytoplasm. When analyzing the transcriptome-wide effects of EJC and RNPS1 knockdowns in different human cell lines, we find no evidence for RNPS1 being a globally essential NMD factor. However, various aberrant splicing events strongly suggest that the main function of RNPS1 is splicing regulation. Rescue analyses revealed that about half of these RNPS1-dependent splicing events was fully or partially rescued by the expression of the isolated RRM domain of RNPS1, whereas other splicing events are regulated by its C-terminal domain. We identified many splicing-regulatory factors, including SR proteins and U1 snRNP components, that specifically interact with the C-terminus or with the RRM 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.Competing Interest StatementThe authors have declared no competing interest.