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.
Pubmed ID: 11546873 RIS Download
3' Untranslated Regions | Active Transport, Cell Nucleus | Cell Line | Codon, Nonsense | DNA-Binding Proteins | Exons | Fungal Proteins | Globins | Humans | Macromolecular Substances | Models, Biological | Precipitin Tests | Protein Binding | RNA Splicing | RNA, Messenger | RNA-Binding Proteins | Recombinant Fusion Proteins | Ribonucleoproteins | Saccharomyces cerevisiae Proteins | Substrate Specificity