Direct and indirect effects of spliceosome disruption compromise gene regulation by nonsense-mediated mRNA decay.

ABSTRACT: Pre-mRNA splicing, carried out in the nucleus by a large ribonucleoprotein machine known as the spliceosome, is functionally and physically coupled to the mRNA surveillance pathway in the cytoplasm called nonsense-mediated mRNA decay (NMD). The NMD pathway monitors for premature translation termination, which can result from alternative splicing, by relying on the exon junction complex (EJC) deposited on exon-exon junctions by the spliceosome. Recently, multiple genetic screens in human cell lines have identified numerous spliceosome components as putative NMD factors. Using publicly available RNA-seq datasets from K562 and HepG2 cells depleted of 18 different spliceosome components, we found that natural NMD-targeted mRNA isoforms were upregulated when catalytic spliceosome members were r

SUBMITTER: Embree CM 

PROVIDER: S-EPMC12427521 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature