UPF1 explained

Regulator of nonsense transcripts 1 is a protein that in humans is encoded by the UPF1 gene.^{[1] [2]}

Function

This gene encodes a protein that is part of a post-splicing multiprotein complex, the exon junction complex, involved in both mRNA nuclear export and mRNA surveillance. 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 is located in both the cytoplasm and nucleus.^[3] When translation ends, it interacts with the functional homolog of yeast Upf2p to trigger mRNA decapping. Use of multiple polyadenylation sites has been noted for this gene.^[4]

Interactions

UPF1 interacts with:

• DCP1A,
• DCP2,^[5]
• SMG1,
• UPF2,^{[6] [7] [8] [9] [10]}
• UPF3A,^{[7] [8] [10]} and
• UPF3B.^{[6] [8] [10]}

Further reading

• Azzalin CM, Lingner J . The double life of UPF1 in RNA and DNA stability pathways . Cell Cycle . 5 . 14 . 1496–8 . 2006 . 16861888 . 10.4161/cc.5.14.3093 . free .
• Horikoshi M, Sekimizu K, Natori S . Analysis of the stimulatory factor of RNA polymerase II in the initiation and elongation complex . J. Biol. Chem. . 259 . 1 . 608–11 . 1984 . 10.1016/S0021-9258(17)43705-7 . 6200476 . free .
• Nagase T, Seki N, Ishikawa K, etal . Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain . DNA Res. . 3 . 5 . 321–9, 341–54 . 1997 . 9039502 . 10.1093/dnares/3.5.321 . free .
• Czaplinski K, Ruiz-Echevarria MJ, Paushkin SV, etal . The surveillance complex interacts with the translation release factors to enhance termination and degrade aberrant mRNAs . Genes Dev. . 12 . 11 . 1665–77 . 1998 . 9620853 . 10.1101/gad.12.11.1665 . 316864 .
• Page MF, Carr B, Anders KR, etal . SMG-2 Is a Phosphorylated Protein Required for mRNA Surveillance in Caenorhabditis elegans and Related to Upf1p of Yeast . Mol. Cell. Biol. . 19 . 9 . 5943–51 . 1999 . 10454541 . 10.1128/MCB.19.9.5943. 84455 .
• Bhattacharya A, Czaplinski K, Trifillis P, etal . Characterization of the biochemical properties of the human Upf1 gene product that is involved in nonsense-mediated mRNA decay . RNA . 6 . 9 . 1226–35 . 2000 . 10999600 . 10.1017/S1355838200000546 . 1369996 .
• Mendell JT, Medghalchi SM, Lake RG, etal . Novel Upf2p Orthologues Suggest a Functional Link between Translation Initiation and Nonsense Surveillance Complexes . Mol. Cell. Biol. . 20 . 23 . 8944–57 . 2000 . 11073994 . 10.1128/MCB.20.23.8944-8957.2000 . 86549 .
• Serin G, Gersappe A, Black JD, etal . 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 . 2001 . 11113196 . 10.1128/MCB.21.1.209-223.2001 . 88795 .
• Lykke-Andersen J, Shu MD, Steitz JA . Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon . Cell . 103 . 7 . 1121–31 . 2001 . 11163187 . 10.1016/S0092-8674(00)00214-2 . 18417600 . free .
• Denning G, Jamieson L, Maquat LE, etal . Cloning of a novel phosphatidylinositol kinase-related kinase: characterization of the human SMG-1 RNA surveillance protein . J. Biol. Chem. . 276 . 25 . 22709–14 . 2001 . 11331269 . 10.1074/jbc.C100144200 . free .
• Yamashita A, Ohnishi T, Kashima I, etal . 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 . 2001 . 11544179 . 10.1101/gad.913001 . 312771 .
• Lykke-Andersen J, Shu MD, Steitz JA . Communication of the position of exon-exon junctions to the mRNA surveillance machinery by the protein RNPS1 . Science . 293 . 5536 . 1836–9 . 2001 . 11546874 . 10.1126/science.1062786 . 2001Sci...293.1836L . 389385 .
• Carastro LM, Tan CK, Selg M, etal . Identification of delta helicase as the bovine homolog of HUPF1: demonstration of an interaction with the third subunit of DNA polymerase delta . Nucleic Acids Res. . 30 . 10 . 2232–43 . 2002 . 12000843 . 10.1093/nar/30.10.2232 . 115286 .
• Mendell JT, ((ap Rhys CM)), Dietz HC . Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts . Science . 298 . 5592 . 419–22 . 2002 . 12228722 . 10.1126/science.1074428 . 46447414 . free .
• Lykke-Andersen J . Identification of a Human Decapping Complex Associated with hUpf Proteins in Nonsense-Mediated Decay . Mol. Cell. Biol. . 22 . 23 . 8114–21 . 2003 . 12417715 . 10.1128/MCB.22.23.8114-8121.2002 . 134073 .
• Strausberg RL, Feingold EA, Grouse LH, etal . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Chiu SY, Serin G, Ohara O, Maquat LE . 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 . 2003 . 12554878 . 10.1261/rna.2137903 . 1370372 .
• Schell T, Köcher T, Wilm M, etal . 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 . 2003 . 12723973 . 10.1042/BJ20021920 . 1223536 .

Notes and References

1. Perlick HA, Medghalchi SM, Spencer FA, ((Kendzior RJ Jr)), Dietz HC . Mammalian orthologues of a yeast regulator of nonsense transcript stability . Proc Natl Acad Sci U S A . 93 . 20 . 10928–32 . November 1996 . 8855285 . 38260 . 10.1073/pnas.93.20.10928 . 1996PNAS...9310928P . free .
2. Applequist SE, Selg M, Raman C, Jack HM . Cloning and characterization of HUPF1, a human homolog of the Saccharomyces cerevisiae nonsense mRNA-reducing UPF1 protein . Nucleic Acids Res . 25 . 4 . 814–21 . March 1997 . 9064659 . 146496 . 10.1093/nar/25.4.814 .
3. Singh AK, Choudhury SR, De S, Zhang J, Kissane S, Dwivedi V, Ramanathan P, Petric M, Orsini L, Hebenstreit D, Brogna S . 6 . The RNA helicase UPF1 associates with mRNAs co-transcriptionally and is required for the release of mRNAs from gene loci . eLife . 8 . e41444 . March 2019 . 30907728 . 10.7554/eLife.41444 . 6447362 . Singer RH, Manley JL . free .
4. Web site: UPF1 UPF1 RNA helicase and ATPase [Homo sapiens (human) ]].
5. Lykke-Andersen J . Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay . Mol. Cell. Biol. . 22 . 23 . 8114–21 . 2002 . 12417715 . 134073 . 10.1128/MCB.22.23.8114-8121.2002.
6. Lejeune F, Li X, Maquat LE . Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities . Mol. Cell . 12 . 3 . 675–87 . 2003 . 14527413 . 10.1016/S1097-2765(03)00349-6. free .
7. Yamashita A, Ohnishi T, Kashima I, Taya Y, Ohno S . 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 . 2001 . 11544179 . 312771 . 10.1101/gad.913001 .
8. Schell T, Köcher T, Wilm M, Seraphin B, Kulozik AE, Hentze MW . 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 . 2003 . 12723973 . 1223536 . 10.1042/BJ20021920 .
9. Mendell JT, Medghalchi SM, Lake RG, Noensie EN, Dietz HC . Novel Upf2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes . Mol. Cell. Biol. . 20 . 23 . 8944–57 . 2000 . 11073994 . 86549 . 10.1128/MCB.20.23.8944-8957.2000.
10. Lykke-Andersen J, Shu MD, Steitz JA . Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon . Cell . 103 . 7 . 1121–31 . 2000 . 11163187 . 10.1016/S0092-8674(00)00214-2. 18417600 . free .