Communication of the Position of Exon-Exon Junctions to the mRNA Surveillance Machinery by the Protein RNPS1

In mammalian cells, splice junctions play a dual role in mRNA quality control: They mediate selective nuclear export of mature mRNA and they serve as a mark for mRNA surveillance, which subjects aberrant mRNAs with premature termination codons to nonsense-mediated decay (NMD). Here, we demonstrate that the protein RNPS1, a component of the postsplicing complex that is deposited 5′ to exon-exon junctions, interacts with the evolutionarily conserved human Upf complex, a central component of NMD. Significantly, RNPS1 triggers NMD when tethered to the 3′ untranslated region of β-globin mRNA, demonstrating its role as a subunit of the postsplicing complex directly involved in mRNA surveillance.