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 beta-globin mRNA, demonstrating its role as a subunit of the postsplicing complex directly involved in mRNA surveillance.
Lykke-Andersen
J
J
Howard Hughes Medical Institute, Molecular Biochemistry and Biophysics, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
Shu
M D
MD
Steitz
J A
JA
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005091:Exons / Q000235:genetics*; D005656:Fungal Proteins / Q000378:metabolism; D005914:Globins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008954:Models, Biological; D011233:Precipitin Tests; D011485:Protein Binding; D020365:RNA Helicases / Q000378:metabolism; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012261:Ribonucleoproteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014162:Transfection
D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D046911:Macromolecular Substances; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C084538:RNPS1 protein, human; D011993:Recombinant Fusion Proteins; C484446:Rent1 protein, mouse; D012261:Ribonucleoproteins; C498284:Rnps1 protein, mouse; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; C096360:UPF3 protein, S cerevisiae; D005914:Globins; D020365:RNA Helicases; C101828:UPF1 protein, human