Host Protein General Information (ID: PT0646)
  Protein Name
Pseudouridylate synthase RPUSD4 (RPUSD4)
  Gene Name
RPUSD4
  Host Species
Homo sapiens
  Uniprot Entry Name
RUSD4_HUMAN
  Protein Families
Pseudouridine synthase RluA family
  EC Number
5.4.99.-
  Subcellular Location
Mitochondrion matrix Nucleus Cytoplasm
  External Link
NCBI Gene ID
84881
Uniprot ID
Q96CM3
Ensembl ID
ENSG00000165526
HGNC ID
HGNC:25898
  Function in Host
Catalyzes uridine to pseudouridine isomerization (pseudouridylation) of different mitochondrial RNA substrates. Acts on position 1397 in 16Smitochondrial ribosomal RNA (16S mt-rRNA). Thismodification is required for the assembly of 16S mt-rRNA into afunctional mitochondrial ribosome. As a component ofa functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mt-rRNA, controls 16S mt-rRNA abundanceand is required for intra-mitochondrial translation. Acts on position 39 in mitochondrial tRNA (Phe). Alsocatalyzes pseudouridylation of mRNAs in nucleus: acts as a regulator ofpre-mRNA splicing by mediating pseudouridylation of pre-mRNAs atlocations associated with alternatively spliced regions. Pseudouridylation of pre-mRNAs near splice sitesdirectly regulates mRNA splicing and mRNA 3'-end processing. [1-3]
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  3D Structure

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [4]
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 RPUSD4 in viral infection, RPUSD4 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 RPUSD4 increases SARS-CoV-2 RNA levels compared with control group.

 Full List of Virus RNA Interacting with This Protien
            RNA Region: Not Specified Virus Region (hCoV-19/England/02/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [5]
              Strains Name
hCoV-19/England/02/2020
              Strains Family
Beta (B.1.351)
              RNA Binding Region
Not Specified Virus Region
              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 Lung
              Infection Time 24 h
              Interaction Score P-adjust = 0.013
              Method Description UV protein-RNA crosslinking; RNA interactome capture (cRIC); RNA antisense purification coupled with mass spectrometry (RAP-MS)

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
MAAPRWSASGPWIRGNGQGCGSLFTLVSKPFCAAAAASTAINAQRLAEKLRAQKREQDTKKEPVSTNAVQRRVQEIVRFTRQLQRVHPNVLAKALTRGILHQDKNLVVINKPYGLPVHGGPGVQLCITDVLPILAKMLHGHKAEPLHLCHRLDKETTGVMVLAWDKDMAHQVQELFRTRQVVKKYWAITVHVPMPSAGVVDIPIVEKEAQGQQQHHKMTLSPSYRMDDGKMVKVRRSRNAQVAVTQYQVLSSTLSSALVELQPITGIKHQLRVHLSFGLDCPILGDHKYSDWNRLAPQKLSVGTLKKLGLEQSKARYIPLHLHARQLILPALGSGKEELNLVCKLPRFFVHSLHRLRLEMPNEDQNENNEAKCLGAQ
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References
1 The Pseudouridine Synthase RPUSD4 Is an Essential Component of Mitochondrial RNA Granules. J Biol Chem. 2017 Mar 17;292(11):4519-4532.
2 A pseudouridine synthase module is essential for mitochondrial protein synthesis and cell viability. EMBO Rep. 2017 Jan;18(1):28-38.
3 A Genome-wide CRISPR Death Screen Identifies Genes Essential for Oxidative Phosphorylation. Cell Metab. 2016 Dec 13;24(6):875-885.
4 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.
5 Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection. Mol Cell. 2021 Jul 1;81(13):2851-2867.e7.