Host Protein General Information (ID: PT0426)
  Protein Name
Exosome complex component RRP41 (EXOSC4)
  Gene Name
EXOSC4
  Host Species
Homo sapiens
  Uniprot Entry Name
EXOS4_HUMAN
  Protein Families
RNase PH family
  Subcellular Location
Cytoplasm Nucleus; nucleolus Nucleus
  External Link
NCBI Gene ID
54512
Uniprot ID
Q9NPD3
Ensembl ID
ENSG00000178896
HGNC ID
HGNC:18189
  Function in Host
Non-catalytic component of the RNA exosome complex which has3'->5' exoribonuclease activity and participates in a multitude ofcellular RNA processing and degradation events. In the nucleus, the RNAexosome complex is involved in proper maturation of stable RNA speciessuch as rRNA, snRNA and snoRNA, in the elimination of RNA processingby-products and non-coding 'pervasive' transcripts, such as antisenseRNA species and promoter-upstream transcripts (PROMPTs), and of mRNAswith processing defects, thereby limiting or excluding their export tothe cytoplasm. The RNA exosome may be involved in Ig class switchrecombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNAsubstrates. In the cytoplasm, the RNA exosome complex is involved ingeneral mRNA turnover and specifically degrades inherently unstablemRNAs containing AU-rich elements (AREs) within their 3' untranslatedregions, and in RNA surveillance pathways, preventing translation ofaberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation ofRNA for ribonucleolysis, and to serve as a scaffold for the associationwith catalytic subunits and accessory proteins or complexes. EXOSC4binds to ARE-containing RNAs. [1-5]
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  Related KEGG Pathway
RNA degradation hsa03018            Pathway Map 
  3D Structure

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [6]
Infected TissueLung Infection Time7-9 Days
Infected CellCalu-3 Cells (Human epithelial cell line) Cellosaurus IDCVCL_0609 
Method DescriptionTo detect the role of host protein EXOSC4 in viral infection, EXOSC4 protein knockout Calu-3 Cells were infected with SARS-COV-2 for 7 - 9 Days , and the effects on infection was detected through CRISPR-based genome-wide gene-knockout screen.
ResultsIt is reported that knockout of EXOSC4 increases SARS-CoV-2 RNA levels compared with control group.

 Full List of Virus RNA Interacting with This Protien
            RNA Region: ORF10 (hCoV-19/Not Specified Virus Strain )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [7]
              Strains Name
hCoV-19/Not Specified Virus Strain
              RNA Binding Region
ORF10
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Calu-3 cells (Human Lung Cancer Cell)  (CVCL_0609 )
              Cell Originated Tissue Liver
              Interaction Score P-value < 0.05
              Method Description RNA pull-down assays; liquid chromatography with tandem mass spectrometry (LC-MS/MS); Wilcoxon test; MS2 affinity purification coupled with liquid chromatography-mass spectrometry (MAMS)

Differential Gene Expression During SARS-COV-2 Infection
GEO Accession: GSE152641
Sample Type: Blood
Samples Details: Healthy Control: 24; COVID-19: 62
Platform: GPL24676 Illumina NovaSeq 6000
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GEO Accession: GSE162835
Sample Type: Nasopharyngeal Swabs
Samples Details: COVID-19 (Mild Symptoms): 37; COVID-19 (Moderate Symptoms): 10; COVID-19 (Severe Symptoms): 3
Platform: GPL24676 Illumina NovaSeq 6000
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GEO Accession: GSE175779
Sample Type: Human Bronchial Epithelial Cells
Samples Details: Healthy Control: 4 (0, 24, 48, 72 and 96 h); COVID-19: 4 (24, 48, 72 and 96 h)
Platform: GPL18573 Illumina NextSeq 500
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Protein Sequence Information
MAGLELLSDQGYRVDGRRAGELRKIQARMGVFAQADGSAYIEQGNTKALAVVYGPHEIRGSRARALPDRALVNCQYSSATFSTGERKRRPHGDRKSCEMGLQLRQTFEAAILTQLHPRSQIDIYVQVLQADGGTYAACVNAATLAVLDAGIPMRDFVCACSAGFVDGTALADLSHVEEAAGGPQLALALLPASGQIALLEMDARLHEDHLERVLEAAAQAARDVHTLLDRVVRQHVREASILLGD
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References
1 Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5 to 3 and 3 to 5 . Genes Dev. 2008 Jan 1;22(1):50-65.
2 The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates. Cell. 2011 Feb 4;144(3):353-63.
3 Addition of poly(A) and poly(A)-rich tails during RNA degradation in the cytoplasm of human cells. Proc Natl Acad Sci USA. 2010 Apr 20;107(16):7407-12.
4 Human cell growth requires a functional cytoplasmic exosome, which is involved in various mRNA decay pathways. RNA. 2007 Jul;13(7):1027-35.
5 Sequence-specific RNA binding mediated by the RNase PH domain of components of the exosome. RNA. 2006 Oct;12(10):1810-6.
6 Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2. Nat Commun. 2022 Apr 25;13(1):2237.
7 Mapping the host protein interactome of non-coding regions in SARS-CoV-2 genome. bioRxiv. 2021 Jun; DOI:10.1101/2021.06.19.449092.