Details of Host Protein

 Host Protein General Information (ID: PT0917)
  Protein Name
Regulator of nonsense transcripts 1 (NORF1)
  Gene Name
UPF1
  Host Species
Homo sapiens
  Uniprot Entry Name
RENT1_HUMAN
  Protein Families
DNA2/NAM7 helicase family
  EC Number
3.6.4.12; 3.6.4.13
  Subcellular Location
Cytoplasm
  External Link
NCBI Gene ID
5976
Uniprot ID
Q92900
Ensembl ID
ENSG00000005007
HGNC ID
HGNC:9962
  Function in Host
RNA-dependent helicase required for nonsense-mediated decay (NMD) of aberrant mRNAs containing premature stop codons and modulatesthe expression level of normal mRNAs. Isrecruited to mRNAs upon translation termination and undergoes a cycleof phosphorylation and dephosphorylation; its phosphorylation appearsto be a key step in NMD. Recruitedby release factors to stalled ribosomes together with the SMG1C proteinkinase complex to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. In EJC-dependent NMD, the SURF complex associateswith the exon junction complex (EJC) (located 50-55 or more nucleotidesdownstream from the termination codon) through UPF2 and allows theformation of an UPF1-UPF2-UPF3 surveillance complex which is believedto activate NMD. Phosphorylated UPF1 is recognized byEST1B/SMG5, SMG6 and SMG7 which are thought to provide a link to themRNA degradation machinery involving exonucleolytic and endonucleolyticpathways, and to serve as adapters to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation and allowing the recycling ofNMD factors. UPF1 can also activate NMD without UPF2or UPF3, and in the absence of the NMD-enhancing downstream EJCindicative for alternative NMD pathways. Plays a rolein replication-dependent histone mRNA degradation at the end of phaseS; the function is independent of UPF2. For the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 andPABPC1 with the ribosome-bound release factors is proposed. The ATPase activity of UPF1 isrequired for disassembly of mRNPs undergoing NMD. Together with UPF2 and dependent on TDRD6, mediates the degradation ofmRNA harboring long 3'UTR by inducing the NMD machinery. Also capable of unwinding double-stranded DNA andtranslocating on single-stranded DNA. [1-9]
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  Related KEGG Pathway
Nucleocytoplasmic transport hsa03013            Pathway Map 
mRNA surveillance pathway hsa03015            Pathway Map 
  3D Structure
PDB ID: 2GJK 
FASTA   Download
  2D PNG Download  
PDB File Download

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Pro-viral [10]
Infected TissueLung Infection Time24 h
Infected CellCalu-3 cells (Human lung cancer cell line) Cellosaurus IDCVCL_0609 
Method DescriptionTo detect the role of host protein UPF1 in viral infection, UPF1 protein knockout Calu-3 cells were infected with SARS-COV-2 for 24 h , and the effects on infection was detected through qRT-PCR.
ResultsIt is reported that Knockdown of UPF1 leads to the reduced SARS-CoV-2 RNA levels compared with control group.

Host Protein - Virus RNA Network
  Network Download  

 Full List of Virus RNA Interacting with This Protien
            RNA Region: 3'-UTR (hCoV-19/IPBCAMS-YL01/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [11]
              Strains Name
hCoV-19/IPBCAMS-YL01/2020
              Strains Family
Beta (B.1.351)
              RNA Binding Region
3'-UTR
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Huh7.5.1 cells (Hepatocyte derived cellular carcinoma cell)  (CVCL_E049 )
              Cell Originated Tissue Liver
              Infection Time 30 h
              Interaction Score Affinity = 1
              Method Description PrismNet; pull-down western (STAR methods); Mass spectrometry
           RNA Region: 5'-UTR (hCoV-19/IPBCAMS-YL01/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [11]
              Strains Name
hCoV-19/IPBCAMS-YL01/2020
              Strains Family
Beta (B.1.351)
              RNA Binding Region
5'-UTR
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Huh7.5.1 cells (Hepatocyte derived cellular carcinoma cell) Huh7.5.1 cells (Hepatocyte derived cellular carcinoma cell)  (CVCL_E049 )
              Cell Originated Tissue Liver
              Infection Time 30 h
              Interaction Score Affinity = 0.982
              Method Description PrismNet; pull-down western (STAR methods); Mass spectrometry
           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 [12]
              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 Huh7 cells (human liver cell line) Huh7 cells (human liver cell line)  (CVCL_0336 )
              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)
           RNA Region: ORF1ab (hCoV-19/Zambia/ZMB-88673/2021 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [13]
              Strains Name
hCoV-19/Zambia/ZMB-88673/2021
              Strains Family
Beta (B.1.351)
              RNA Binding Region
ORF1ab
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Infection Cells HepG2 cells (hepatocellular carcinoma cell line) HepG2 cells (hepatocellular carcinoma cell line)  (CVCL_0027 )
              Cell Originated Tissue Liver
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: ORF1ab (hCoV-19/Wuhan/WHUH020/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [13]
              Strains Name
hCoV-19/Wuhan/WHUH020/2020
              Strains Family
Epsilon (B.1.427; B.1.429)
              RNA Binding Region
ORF1ab
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Infection Cells HepG2 cells (hepatocellular carcinoma cell line) HepG2 cells (hepatocellular carcinoma cell line)  (CVCL_0027 )
              Cell Originated Tissue Liver
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: ORF1ab (hCoV-19/USA/CA-CZB-14678/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [13]
              Strains Name
hCoV-19/USA/CA-CZB-14678/2020
              Strains Family
Epsilon (B.1.427; B.1.429)
              RNA Binding Region
ORF1ab
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Infection Cells HepG2 cells (hepatocellular carcinoma cell line) HepG2 cells (hepatocellular carcinoma cell line)  (CVCL_0027 )
              Cell Originated Tissue Liver
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: ORF1ab (hCoV-19/NewZealand/20CV0676/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [13]
              Strains Name
hCoV-19/NewZealand/20CV0676/2020
              Strains Family
Epsilon (B.1.427; B.1.429)
              RNA Binding Region
ORF1ab
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Infection Cells HepG2 cells (hepatocellular carcinoma cell line) HepG2 cells (hepatocellular carcinoma cell line)  (CVCL_0027 )
              Cell Originated Tissue Liver
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: ORF1ab (hCoV-19/Malawi/KRISP-K010154/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [13]
              Strains Name
hCoV-19/Malawi/KRISP-K010154/2020
              Strains Family
Beta (B.1.351)
              RNA Binding Region
ORF1ab
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Infection Cells HepG2 cells (hepatocellular carcinoma cell line) HepG2 cells (hepatocellular carcinoma cell line)  (CVCL_0027 )
              Cell Originated Tissue Liver
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: ORF1ab (hCoV-19/Guam/GU-CDC-2-3906081-/2021 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [13]
              Strains Name
hCoV-19/Guam/GU-CDC-2-3906081-/2021
              Strains Family
Epsilon (B.1.427; B.1.429)
              RNA Binding Region
ORF1ab
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Infection Cells HepG2 cells (hepatocellular carcinoma cell line) HepG2 cells (hepatocellular carcinoma cell line)  (CVCL_0027 )
              Cell Originated Tissue Liver
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: ORF1ab (hCoV-19/Eswatini/N2779/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [13]
              Strains Name
hCoV-19/Eswatini/N2779/2020
              Strains Family
Beta (B.1.351)
              RNA Binding Region
ORF1ab
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Infection Cells HepG2 cells (hepatocellular carcinoma cell line) HepG2 cells (hepatocellular carcinoma cell line)  (CVCL_0027 )
              Cell Originated Tissue Liver
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: N region (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [13]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
N region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Infection Cells HepG2 cells (hepatocellular carcinoma cell line) HepG2 cells (hepatocellular carcinoma cell line)  (CVCL_0027 )
              Cell Originated Tissue Liver
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: Not Specified Virus Region (hCoV-SARS/Manitoba/2003 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [13]
              Strains Name
hCoV-SARS/Manitoba/2003
              Strains Family
Beta
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Severe acute respiratory syndrome-related coronavirus (HCoV-SARS)
              Interaction Type Potential binding protein
              Infection Cells HepG2 cells (hepatocellular carcinoma cell line) HepG2 cells (hepatocellular carcinoma cell line)  (CVCL_0027 )
              Cell Originated Tissue Liver
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: Not Specified Virus Region (hCov-OC43/VR-759 Quebec/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [13]
              Strains Name
hCov-OC43/VR-759 Quebec/2019
              Strains Family
Beta
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Human coronavirus OC43 (HCov-OC43)
              Interaction Type Potential binding protein
              Infection Cells HepG2 cells (hepatocellular carcinoma cell line) HepG2 cells (hepatocellular carcinoma cell line)  (CVCL_0027 )
              Cell Originated Tissue Liver
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: Not Specified Virus Region (hCov-NL63/Amsterdam/2004 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [13]
              Strains Name
hCov-NL63/Amsterdam/2004
              Strains Family
Alpha
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Human Coronavirus NL63 (HCov-NL63)
              Interaction Type Potential binding protein
              Infection Cells HepG2 cells (hepatocellular carcinoma cell line) HepG2 cells (hepatocellular carcinoma cell line)  (CVCL_0027 )
              Cell Originated Tissue Liver
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: Not Specified Virus Region (hCov-MERS/Jeddah/2012 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [13]
              Strains Name
hCov-MERS/Jeddah/2012
              Strains Family
Beta
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Middle East respiratory syndrome-related coronavirus (HCov-MERS)
              Interaction Type Potential binding protein
              Infection Cells HepG2 cells (hepatocellular carcinoma cell line) HepG2 cells (hepatocellular carcinoma cell line)  (CVCL_0027 )
              Cell Originated Tissue Liver
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: Not Specified Virus Region (hCoV-HKU1/Hong Kong/2004 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [13]
              Strains Name
hCoV-HKU1/Hong Kong/2004
              Strains Family
Beta
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Human coronavirus HKU1 (HCoV-HKU1)
              Interaction Type Potential binding protein
              Infection Cells HepG2 cells (hepatocellular carcinoma cell line) HepG2 cells (hepatocellular carcinoma cell line)  (CVCL_0027 )
              Cell Originated Tissue Liver
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: Not Specified Virus Region (hCov-229E/Würzburg/2000 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [13]
              Strains Name
hCov-229E/Würzburg/2000
              Strains Family
Alpha
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Human coronavirus 229E (HCov-229E)
              Interaction Type Potential binding protein
              Infection Cells HepG2 cells (hepatocellular carcinoma cell line) HepG2 cells (hepatocellular carcinoma cell line)  (CVCL_0027 )
              Cell Originated Tissue Liver
              Method Description ENCODE project database; Pysster model; DeepRiPe (Section 3.6; 3.7; 3.8; 3.9); ClustalO (72) algorithm
           RNA Region: Not Specified Virus Region (hCoV-19/Not Specified Virus Strain )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [14]
              Strains Name
hCoV-19/Not Specified Virus Strain
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Huh7 cells (liver carcinoma cell) Huh7 cells (liver carcinoma cell)  (CVCL_0336 )
              Cell Originated Tissue Liver
              Infection Time 24h
              Interaction Score log2FC = 3.81824E+14
              Method Description RNA antisense purification and quantitative mass spectrometry (RAP-MS); Tandem mass tag (TMT) labelling; liquid chromatography tandem mass spectrometry (LC-MS/MS); Westernblot
           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 [15]
              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) Calu-3 cells (Human lung cancer cell)  (CVCL_0609 )
              Cell Originated Tissue Lung
              Infection Time 24 h
              Interaction Score P-adjust = 0.006
              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
  PNG Download  
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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
  PNG Download  
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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
  PNG Download  
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Protein Phosphorylation after Virus Infection
S1107 [16]
  PNG Download  
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S1127 [17]
  PNG Download  
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S1127 [16]
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Protein Sequence Information
MSVEAYGPSSQTLTFLDTEEAELLGADTQGSEFEFTDFTLPSQTQTPPGGPGGPGGGGAGGPGGAGAGAAAGQLDAQVGPEGILQNGAVDDSVAKTSQLLAELNFEEDEEDTYYTKDLPIHACSYCGIHDPACVVYCNTSKKWFCNGRGNTSGSHIVNHLVRAKCKEVTLHKDGPLGETVLECYNCGCRNVFLLGFIPAKADSVVVLLCRQPCASQSSLKDINWDSSQWQPLIQDRCFLSWLVKIPSEQEQLRARQITAQQINKLEELWKENPSATLEDLEKPGVDEEPQHVLLRYEDAYQYQNIFGPLVKLEADYDKKLKESQTQDNITVRWDLGLNKKRIAYFTLPKTDSGNEDLVIIWLRDMRLMQGDEICLRYKGDLAPLWKGIGHVIKVPDNYGDEIAIELRSSVGAPVEVTHNFQVDFVWKSTSFDRMQSALKTFAVDETSVSGYIYHKLLGHEVEDVIIKCQLPKRFTAQGLPDLNHSQVYAVKTVLQRPLSLIQGPPGTGKTVTSATIVYHLARQGNGPVLVCAPSNIAVDQLTEKIHQTGLKVVRLCAKSREAIDSPVSFLALHNQIRNMDSMPELQKLQQLKDETGELSSADEKRYRALKRTAERELLMNADVICCTCVGAGDPRLAKMQFRSILIDESTQATEPECMVPVVLGAKQLILVGDHCQLGPVVMCKKAAKAGLSQSLFERLVVLGIRPIRLQVQYRMHPALSAFPSNIFYEGSLQNGVTAADRVKKGFDFQWPQPDKPMFFYVTQGQEEIASSGTSYLNRTEAANVEKITTKLLKAGAKPDQIGIITPYEGQRSYLVQYMQFSGSLHTKLYQEVEIASVDAFQGREKDFIILSCVRANEHQGIGFLNDPRRLNVALTRARYGVIIVGNPKALSKQPLWNHLLNYYKEQKVLVEGPLNNLRESLMQFSKPRKLVNTINPGARFMTTAMYDAREAIIPGSVYDRSSQGRPSSMYFQTHDQIGMISAGPSHVAAMNIPIPFNLVMPPMPPPGYFGQANGPAAGRGTPKGKTGRGGRQKNRFGLPGPSQTNLPNSQASQDVASQPFSQGALTQGYISMSQPSQMSQPGLSQPELSQDSYLGDEFKSQIDVALSQDSTYQGERAYQHGGVTGLSQY
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References
1 MOV10 Is a 5 to 3 RNA helicase contributing to UPF1 mRNA target degradation by translocation along 3 UTRs. Mol Cell. 2014 May 22;54(4):573-85.
2 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.
3 The RNA helicase DHX34 activates NMD by promoting a transition from the surveillance to the decay-inducing complex. Cell Rep. 2014 Sep 25;8(6):1845-1856.
4 Molecular mechanisms for the RNA-dependent ATPase activity of Upf1 and its regulation by Upf2. Mol Cell. 2011 Mar 18;41(6):693-703.
5 Upf1 ATPase-dependent mRNP disassembly is required for completion of nonsense- mediated mRNA decay. Cell. 2010 Dec 10;143(6):938-50.
6 SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate remodeling of the mRNA surveillance complex during nonsense-mediated mRNA decay. Genes Dev. 2009 May 1;23(9):1091-105.
7 Regulated degradation of replication-dependent histone mRNAs requires both ATR and Upf1. Nat Struct Mol Biol. 2005 Sep;12(9):794-800.
8 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. 2001 Sep 1;15(17):2215-28.
9 Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon. Cell. 2000 Dec 22;103(7):1121-31.
10 The SARS-CoV-2 RNA interactome. Mol Cell. 2021 Jul 1;81(13):2838-2850.e6.
11 In vivo structural characterization of the SARS-CoV-2 RNA genome identifies host proteins vulnerable to repurposed drugs. Cell. 2021 Apr 1;184(7):1865-1883.e20.
12 Mapping the host protein interactome of non-coding regions in SARS-CoV-2 genome. bioRxiv. 2021 Jun; DOI:10.1101/2021.06.19.449092.
13 Computational Mapping of the Human-SARS-CoV-2 Protein-RNA Interactome. bioRxiv. 2021 Dec; DOI:.org/10.1101/2021.12.22.472458.
14 The SARS-CoV-2 RNA-protein interactome in infected human cells. Nat Microbiol. 2021 Mar;6(3):339-353.
15 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.
16 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.
17 The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 Aug 6;182(3):685-712.e19.