UPF2

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UPF2
Protein UPF2 PDB 1uw4.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases UPF2 , HRENT2, smg-3, UPF2 regulator of nonsense transcripts homolog (yeast), regulator of nonsense mediated mRNA decay, UPF2 regulator of nonsense mediated mRNA decay
External IDs OMIM: 605529 MGI: 2449307 HomoloGene: 6101 GeneCards: UPF2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_015542
NM_080599

NM_001081132

RefSeq (protein)

NP_056357
NP_542166

NP_001074601

Location (UCSC) Chr 10: 11.92 – 12.04 Mb Chr 2: 5.96 – 6.06 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Regulator of nonsense transcripts 2 is a protein that in humans is encoded by the UPF2 gene. [5] [6] [7]

Contents

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. [7] UPF2 has recently been shown to alter adult behavior via alterations in hippocampal synaptic spine density and the late long-term potentiation of neurons. [8]

Interactions

UPF2 has been shown to interact with UPF1, [5] [9] [10] [11] [12] UPF3A [9] [12] and UPF3B. [9] [12] [13] [14]

Related Research Articles

<span class="mw-page-title-main">Nonsense-mediated decay</span> Elimination of mRNA with premature stop codons in eukaryotes

Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that exists in all eukaryotes. Its main function is to reduce errors in gene expression by eliminating mRNA transcripts that contain premature stop codons. Translation of these aberrant mRNAs could, in some cases, lead to deleterious gain-of-function or dominant-negative activity of the resulting proteins.

P-bodies, or processing bodies are distinct foci formed by phase separation within the cytoplasm of the eukaryotic cell consisting of many enzymes involved in mRNA turnover. P-bodies are highly conserved structures and have been observed in somatic cells originating from vertebrates and invertebrates, plants and yeast. To date, P-bodies have been demonstrated to play fundamental roles in general mRNA decay, nonsense-mediated mRNA decay, adenylate-uridylate-rich element mediated mRNA decay, and microRNA (miRNA) induced mRNA silencing. Not all mRNAs which enter P-bodies are degraded, as it has been demonstrated that some mRNAs can exit P-bodies and re-initiate translation. Purification and sequencing of the mRNA from purified processing bodies showed that these mRNAs are largely translationally repressed upstream of translation initiation and are protected from 5' mRNA decay.

<span class="mw-page-title-main">Cap binding complex</span> Formation on 5 ends of mRNAs

The 5' cap of eukaryotic messenger RNA is bound at all times by various cap-binding complexes (CBCs).

<span class="mw-page-title-main">RBM8A</span> Protein-coding gene in the species Homo sapiens

RNA-binding protein 8A is a protein that in humans is encoded by the RBM8A gene.

<span class="mw-page-title-main">UPF1</span> Protein-coding gene in the species Homo sapiens

Regulator of nonsense transcripts 1 is a protein that in humans is encoded by the UPF1 gene.

<span class="mw-page-title-main">SRRM1</span> Protein-coding gene in the species Homo sapiens

Serine/arginine repetitive matrix protein 1 is a protein that in humans is encoded by the SRRM1 gene.

<span class="mw-page-title-main">RNPS1</span>

RNA-binding protein with serine-rich domain 1 is a protein that in humans is encoded by the RNPS1 gene.

<span class="mw-page-title-main">UPF3B</span> Protein-coding gene in the species Homo sapiens

Regulator of nonsense transcripts 3B is a protein that in humans is encoded by the UPF3B gene.

<span class="mw-page-title-main">DCP2</span> Protein found in humans

mRNA-decapping enzyme 2 is a protein that in humans is encoded by the DCP2 gene.

<span class="mw-page-title-main">SMG1</span>

Serine/threonine-protein kinase SMG1 is an enzyme that in humans is encoded by the SMG1 gene. SMG1 belongs to the phosphatidylinositol 3-kinase-related kinase protein family.

<span class="mw-page-title-main">CASC3</span> Protein-coding gene in the species Homo sapiens

Protein CASC3 is a protein that in humans is encoded by the CASC3 gene.

<span class="mw-page-title-main">UPF3A</span> 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.

<span class="mw-page-title-main">SMG6</span>

Telomerase-binding protein EST1A is an enzyme that in humans is encoded by the SMG6 gene on chromosome 17. It is ubiquitously expressed in many tissues and cell types. The C-terminus of the EST1A protein contains a PilT N-terminus (PIN) domain. This structure for this domain has been determined by X-ray crystallography. SMG6 functions to bind single-stranded DNA in telomere maintenance and single-stranded RNA in nonsense-mediated mRNA decay (NMD). The SMG6 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.

<span class="mw-page-title-main">SMG5</span> Protein-coding gene in the species Homo sapiens

Protein SMG5 is a protein that in humans is encoded by the SMG5 gene. This protein contains a PIN domain that appears to have mutated the residues in the active site.

<span class="mw-page-title-main">DCP1A</span> Protein found in humans

mRNA-decapping enzyme 1A is a protein that in humans is encoded by the DCP1A gene.

<span class="mw-page-title-main">SMG7</span> Protein-coding gene in the species Homo sapiens

Protein SMG7 is a protein that in humans is encoded by the SMG7 gene.

<span class="mw-page-title-main">DCP1B</span> Protein found in humans

mRNA-decapping enzyme 1B is a protein that in humans is encoded by the DCP1B gene.

<span class="mw-page-title-main">Decapping complex</span> Eukaryotic protein complex that removes the 5 cap on mRNA

The mRNA decapping complex is a protein complex in eukaryotic cells responsible for removal of the 5' cap. The active enzyme of the decapping complex is the bilobed Nudix family enzyme Dcp2, which hydrolyzes 5' cap and releases 7mGDP and a 5'-monophosphorylated mRNA. This decapped mRNA is inhibited for translation and will be degraded by exonucleases. The core decapping complex is conserved in eukaryotes. Dcp2 is activated by Decapping Protein 1 (Dcp1) and in higher eukaryotes joined by the scaffold protein VCS. Together with many other accessory proteins, the decapping complex assembles in P-bodies in the cytoplasm.

mRNA surveillance mechanisms are pathways utilized by organisms to ensure fidelity and quality of messenger RNA (mRNA) molecules. There are a number of surveillance mechanisms present within cells. These mechanisms function at various steps of the mRNA biogenesis pathway to detect and degrade transcripts that have not properly been processed.

<span class="mw-page-title-main">Exon junction complex</span> Protein complex assembled on mRNA

An exon junction complex (EJC) is a protein complex which forms on a pre-messenger RNA strand at the junction of two exons which have been joined together during RNA splicing. The EJC has major influences on translation, surveillance and localization of the spliced mRNA. It is first deposited onto mRNA during splicing and is then transported into the cytoplasm. There it plays a major role in post-transcriptional regulation of mRNA. It is believed that exon junction complexes provide a position-specific memory of the splicing event. The EJC consists of a stable heterotetramer core, which serves as a binding platform for other factors necessary for the mRNA pathway. The core of the EJC contains the protein eukaryotic initiation factor 4A-III bound to an adenosine triphosphate (ATP) analog, as well as the additional proteins Magoh and Y14. The binding of these proteins to nuclear speckled domains has been measured recently and it may be regulated by PI3K/AKT/mTOR signaling pathways. In order for the binding of the complex to the mRNA to occur, the eIF4AIII factor is inhibited, stopping the hydrolysis of ATP. This recognizes EJC as an ATP dependent complex. EJC also interacts with a large number of additional proteins; most notably SR proteins. These interactions are suggested to be important for mRNA compaction. The role of EJC in mRNA export is controversial.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000151461 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000043241 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 Mendell JT, Medghalchi SM, Lake RG, Noensie EN, Dietz HC (Dec 2000). "Novel Upf2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes". Molecular and Cellular Biology. 20 (23): 8944–57. doi:10.1128/MCB.20.23.8944-8957.2000. PMC   86549 . PMID   11073994.
  6. Serin G, Gersappe A, Black JD, Aronoff R, Maquat LE (Jan 2001). "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. doi:10.1128/MCB.21.1.209-223.2001. PMC   88795 . PMID   11113196.
  7. 1 2 "Entrez Gene: UPF2 UPF2 regulator of nonsense transcripts homolog (yeast)".
  8. 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): 3360–3379. doi: 10.1038/s41380-019-0547-5 . ISSN   1476-5578. PMC   7566522 . PMID   31636381. S2CID   204812259.
  9. 1 2 3 Lejeune F, Li X, Maquat LE (Sep 2003). "Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities". Molecular Cell. 12 (3): 675–87. doi: 10.1016/S1097-2765(03)00349-6 . PMID   14527413.
  10. Schell T, Köcher T, Wilm M, Seraphin B, Kulozik AE, Hentze MW (Aug 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". The Biochemical Journal. 373 (Pt 3): 775–83. doi:10.1042/BJ20021920. PMC   1223536 . PMID   12723973.
  11. Yamashita A, Ohnishi T, Kashima I, Taya Y, Ohno S (Sep 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 & Development. 15 (17): 2215–28. doi:10.1101/gad.913001. PMC   312771 . PMID   11544179.
  12. 1 2 3 Lykke-Andersen J, Shu MD, Steitz JA (Dec 2000). "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.
  13. Lehner B, Sanderson CM (Jul 2004). "A protein interaction framework for human mRNA degradation". Genome Research. 14 (7): 1315–23. doi:10.1101/gr.2122004. PMC   442147 . PMID   15231747.
  14. Lykke-Andersen J (Dec 2002). "Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay". Molecular and Cellular Biology. 22 (23): 8114–21. doi:10.1128/MCB.22.23.8114-8121.2002. PMC   134073 . PMID   12417715.

Further reading