Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex.
Nonsense-mediated messenger RNA (mRNA) decay, or NMD, is a critical process of selective degradation of mRNAs that contain premature stop codons. NMD depends on both pre-mRNA splicing and translation, and it requires recognition of the position of stop codons relative to exon-exon junctions. A key factor in NMD is hUpf3, a mostly nuclear protein that shuttles between the nucleus and cytoplasm and interacts specifically with spliced mRNAs. We found that hUpf3 interacts with Y14, a component of post-splicing mRNA-protein (mRNP) complexes, and that hUpf3 is enriched in Y14-containing mRNP complexes. The mRNA export factors Aly/REF and TAP are also associated with nuclear hUpf3, indicating that hUpf3 is in mRNP complexes that are poised for nuclear export. Like Y14 and Aly/REF, hUpf3 binds to spliced mRNAs specifically ( approximately 20 nucleotides) upstream of exon-exon junctions. The splicing-dependent binding of hUpf3 to mRNAs before export, as part of the complex that assembles near exon-exon junctions, allows it to serve as a link between splicing and NMD in the cytoplasm.
Kim
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Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Kataoka
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Dreyfuss
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D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D002460:Cell Line; D018389:Codon, Nonsense / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005914:Globins / Q000235:genetics; D006801:Humans; D046911:Macromolecular Substances; D008954:Models, Biological; D011233:Precipitin Tests; D011485:Protein Binding; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013379:Substrate Specificity
D020413:3' Untranslated Regions; D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D046911:Macromolecular Substances; C406243:RBM8A protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C084538:RNPS1 protein, human; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; D029701:Saccharomyces cerevisiae Proteins; C096360:UPF3 protein, S cerevisiae; C435487:UPF3A protein, human; C435488:UPF3B protein, human; C026452:messenger ribonucleoprotein; D005914:Globins