Protein-coding gene in the species Homo sapiens
Regulator of nonsense transcripts 3A is a protein that in humans is encoded by the UPF3A gene .[4] [5] [6]
This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance . The encoded protein is one of two functional homologs to yeast Upf3p. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons . This protein binds to the mRNA and remains bound after nuclear export, acting as a nucleocytoplasmic shuttling protein . It forms with RBM8A a complex that binds specifically 20 nt upstream of exon-exon junctions. This gene is located on the long arm of chromosome 13. Two splice variants encoding different isoforms have been found for this gene.[6]
Interactions UPF3A has been shown to interact with RBM8A ,[7] UPF2 [5] [8] UPF1 .[5] [9] [10]
References
^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038398 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ Serin G, Gersappe A, Black JD, Aronoff R, Maquat LE (January 2001). "Identification and characterization of human orthologues to Saccharomyces cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis elegans SMG-4)" . Mol Cell Biol . 21 (1): 209–23. doi :10.1128/MCB.21.1.209-223.2001 . PMC 88795 PMID 11113196 . ^ a b c Lykke-Andersen J, Shu MD, Steitz JA (February 2001). "Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon" . Cell . 103 (7): 1121–31. doi :10.1016/S0092-8674(00)00214-2 PMID 11163187 . S2CID 18417600 . ^ a b "Entrez Gene: UPF3A UPF3 regulator of nonsense transcripts homolog A (yeast)" .^ Kim, V N; Kataoka N; Dreyfuss G (September 2001). "Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex". Science 293 (5536): 1832–6. Bibcode :2001Sci...293.1832K . doi :10.1126/science.1062829 . ISSN 0036-8075 . PMID 11546873 . S2CID 12018200 . ^ Lejeune, Fabrice; Li Xiaojie; Maquat Lynne E (September 2003). "Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities" . Mol. Cell . 12 (3): 675–87. doi :10.1016/S1097-2765(03)00349-6 ISSN 1097-2765 . PMID 14527413 . ^ Schell, Thomas; Köcher Thomas; Wilm Matthias; Seraphin Bertrand; Kulozik Andreas E; Hentze Matthias W (August 2003). "Complexes between the nonsense-mediated mRNA decay pathway factor human upf1 (up-frameshift protein 1) and essential nonsense-mediated mRNA decay factors in HeLa cells" . Biochem. J . 373 (Pt 3): 775–83. doi :10.1042/BJ20021920 . ISSN 0264-6021 . PMC 1223536 PMID 12723973 . ^ Yamashita, A; Ohnishi T; Kashima I; Taya Y; Ohno S (September 2001). "Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay" . Genes Dev . 15 (17): 2215–28. doi :10.1101/gad.913001 . ISSN 0890-9369 . PMC 312771 PMID 11544179 .
Further reading
Yamashita A, Ohnishi T, Kashima I, et al. (2001). "Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay" . Genes Dev . 15 (17): 2215–28. doi :10.1101/gad.913001 . PMC 312771 PMID 11544179 . Kim VN, Kataoka N, Dreyfuss G (2001). "Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex". Science . 293 (5536): 1832–6. Bibcode :2001Sci...293.1832K . doi :10.1126/science.1062829 . PMID 11546873 . S2CID 12018200 . Lykke-Andersen J, Shu MD, Steitz JA (2001). "Communication of the position of exon-exon junctions to the mRNA surveillance machinery by the protein RNPS1". Science . 293 (5536): 1836–9. Bibcode :2001Sci...293.1836L . doi :10.1126/science.1062786 . PMID 11546874 . S2CID 389385 . Lykke-Andersen J (2003). "Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay" . Mol. Cell. Biol . 22 (23): 8114–21. doi :10.1128/MCB.22.23.8114-8121.2002 . PMC 134073 PMID 12417715 . Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences" . Proc. Natl. Acad. Sci. U.S.A . 99 (26): 16899–903. Bibcode :2002PNAS...9916899M . doi :10.1073/pnas.242603899 PMC 139241 PMID 12477932 . Chiu SY, Serin G, Ohara O, Maquat LE (2003). "Characterization of human Smg5/7a: a protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1" . RNA . 9 (1): 77–87. doi :10.1261/rna.2137903 . PMC 1370372 PMID 12554878 . Lejeune F, Li X, Maquat LE (2003). "Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities" . Mol. Cell . 12 (3): 675–87. doi :10.1016/S1097-2765(03)00349-6 PMID 14527413 . Ohnishi T, Yamashita A, Kashima I, et al. (2004). "Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7" . Mol. Cell . 12 (5): 1187–200. doi :10.1016/S1097-2765(03)00443-X PMID 14636577 . Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs" . Nat. Genet . 36 (1): 40–5. doi :10.1038/ng1285 PMID 14702039 . Kadlec J, Izaurralde E, Cusack S (2004). "The structural basis for the interaction between nonsense-mediated mRNA decay factors UPF2 and UPF3". Nat. Struct. Mol. Biol . 11 (4): 330–7. doi :10.1038/nsmb741 . PMID 15004547 . S2CID 23042477 . Dunham A, Matthews LH, Burton J, et al. (2004). "The DNA sequence and analysis of human chromosome 13" . Nature . 428 (6982): 522–8. Bibcode :2004Natur.428..522D . doi :10.1038/nature02379 . PMC 2665288 PMID 15057823 . Lehner B, Sanderson CM (2004). "A protein interaction framework for human mRNA degradation" . Genome Res . 14 (7): 1315–23. doi :10.1101/gr.2122004 . PMC 442147 PMID 15231747 . Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)" . Genome Res . 14 (10B): 2121–7. doi :10.1101/gr.2596504 . PMC 528928 PMID 15489334 . Kunz JB, Neu-Yilik G, Hentze MW, et al. (2006). "Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation" . RNA . 12 (6): 1015–22. doi :10.1261/rna.12506 . PMC 1464862 PMID 16601204 . Tarpey PS, Raymond FL, Nguyen LS, et al. (2007). "Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation" . Nat. Genet . 39 (9): 1127–33. doi :10.1038/ng2100 . PMC 2872770 PMID 17704778 . Singh G, Jakob S, Kleedehn MG, Lykke-Andersen J (2007). "Communication with the exon-junction complex and activation of nonsense-mediated decay by human Upf proteins occur in the cytoplasm" . Mol. Cell . 27 (5): 780–92. doi :10.1016/j.molcel.2007.06.030 PMID 17803942 .
