UPF2 explained

Regulator of nonsense transcripts 2 is a protein that in humans is encoded by the UPF2 gene.^{[1] [2] [3]}

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 the perinuclear area. It interacts with translation release factors and the proteins that are functional homologs of yeast Upf1p and Upf3p. Two splice variants have been found for this gene; both variants encode the same protein. UPF2 has recently been shown to alter adult behavior via alterations in hippocampal synaptic spine density and the late long-term potentiation of neurons.^[4]

Interactions

UPF2 has been shown to interact with UPF1,^{[5] [6] [7] [8]} UPF3A^{[5] [8]} and UPF3B.^{[5] [8] [9] [10]}

Further reading

• Wilson KF, Fortes P, Singh US, Ohno M, Mattaj IW, Cerione RA . The nuclear cap-binding complex is a novel target of growth factor receptor-coupled signal transduction . The Journal of Biological Chemistry . 274 . 7 . 4166–73 . Feb 1999 . 9933612 . 10.1074/jbc.274.7.4166 . free .
• Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O . Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 7 . 1 . 65–73 . Feb 2000 . 10718198 . 10.1093/dnares/7.1.65 . free .
• 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 . Dec 2000 . 11163187 . 10.1016/S0092-8674(00)00214-2 . 18417600 . free .
• 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 & Development . 15 . 17 . 2215–28 . Sep 2001 . 11544179 . 312771 . 10.1101/gad.913001 .
• 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 . Sep 2001 . 11546874 . 10.1126/science.1062786 . 2001Sci...293.1836L . 389385 .
• Lejeune F, Ishigaki Y, Li X, Maquat LE . The exon junction complex is detected on CBP80-bound but not eIF4E-bound mRNA in mammalian cells: dynamics of mRNP remodeling . The EMBO Journal . 21 . 13 . 3536–45 . Jul 2002 . 12093754 . 126094 . 10.1093/emboj/cdf345 .
• Lykke-Andersen J . Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay . Molecular and Cellular Biology . 22 . 23 . 8114–21 . Dec 2002 . 12417715 . 134073 . 10.1128/MCB.22.23.8114-8121.2002 .
• 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 . Jan 2003 . 12554878 . 1370372 . 10.1261/rna.2137903 .
• Gehring NH, Neu-Yilik G, Schell T, Hentze MW, Kulozik AE . Y14 and hUpf3b form an NMD-activating complex . Molecular Cell . 11 . 4 . 939–49 . Apr 2003 . 12718880 . 10.1016/S1097-2765(03)00142-4 . free .
• 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 . The Biochemical Journal . 373 . Pt 3 . 775–83 . Aug 2003 . 12723973 . 1223536 . 10.1042/BJ20021920 .
• Lejeune F, Li X, Maquat LE . Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities . Molecular Cell . 12 . 3 . 675–87 . Sep 2003 . 14527413 . 10.1016/S1097-2765(03)00349-6 . free .
• Ohnishi T, Yamashita A, Kashima I, Schell T, Anders KR, Grimson A, Hachiya T, Hentze MW, Anderson P, Ohno S . Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7 . Molecular Cell . 12 . 5 . 1187–200 . Nov 2003 . 14636577 . 10.1016/S1097-2765(03)00443-X . free .
• Kadlec J, Izaurralde E, Cusack S . The structural basis for the interaction between nonsense-mediated mRNA decay factors UPF2 and UPF3 . Nature Structural & Molecular Biology . 11 . 4 . 330–7 . Apr 2004 . 15004547 . 10.1038/nsmb741 . 23042477 .
• Lehner B, Sanderson CM . A protein interaction framework for human mRNA degradation . Genome Research . 14 . 7 . 1315–23 . Jul 2004 . 15231747 . 442147 . 10.1101/gr.2122004 .
• Lejeune F, Ranganathan AC, Maquat LE . eIF4G is required for the pioneer round of translation in mammalian cells . Nature Structural & Molecular Biology . 11 . 10 . 992–1000 . Oct 2004 . 15361857 . 10.1038/nsmb824 . 3093989 .

Notes and References

1. Mendell JT, Medghalchi SM, Lake RG, Noensie EN, Dietz HC . Novel Upf2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes . Molecular and Cellular Biology . 20 . 23 . 8944–57 . Dec 2000 . 11073994 . 86549 . 10.1128/MCB.20.23.8944-8957.2000 .
2. Serin G, Gersappe A, Black JD, Aronoff R, Maquat LE . Identification and characterization of human orthologues to Saccharomyces cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis elegans SMG-4) . Molecular and Cellular Biology . 21 . 1 . 209–23 . Jan 2001 . 11113196 . 88795 . 10.1128/MCB.21.1.209-223.2001 .
3. Web site: Entrez Gene: UPF2 UPF2 regulator of nonsense transcripts homolog (yeast).
4. Notaras. Michael. Allen. Megan. Longo. Francesco. Volk. Nicole. Toth. Miklos. Li Jeon. Noo. Klann. Eric. Colak. Dilek. 2019-10-21. UPF2 leads to degradation of dendritically targeted mRNAs to regulate synaptic plasticity and cognitive function. Molecular Psychiatry. 25. 12. en. 3360–3379. 10.1038/s41380-019-0547-5. 31636381. 7566522. 204812259. 1476-5578. free.
5. Lejeune F, Li X, Maquat LE . Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities . Molecular Cell . 12 . 3 . 675–87 . Sep 2003 . 14527413 . 10.1016/S1097-2765(03)00349-6 . free .
6. 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 . The Biochemical Journal . 373 . Pt 3 . 775–83 . Aug 2003 . 12723973 . 1223536 . 10.1042/BJ20021920 .
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 & Development . 15 . 17 . 2215–28 . Sep 2001 . 11544179 . 312771 . 10.1101/gad.913001 .
8. 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 . Dec 2000 . 11163187 . 10.1016/S0092-8674(00)00214-2 . 18417600 . free .
9. Lehner B, Sanderson CM . A protein interaction framework for human mRNA degradation . Genome Research . 14 . 7 . 1315–23 . Jul 2004 . 15231747 . 442147 . 10.1101/gr.2122004 .
10. Lykke-Andersen J . Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay . Molecular and Cellular Biology . 22 . 23 . 8114–21 . Dec 2002 . 12417715 . 134073 . 10.1128/MCB.22.23.8114-8121.2002 .