Low expression of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication

Moll, Tobias; Odon, Valerie; Harvey, Calum; Collins, Mark O.; Peden, Andrew A.; Franklin, John; Marshall, Jack N G; Souza, Cleide dos Santos; Zhang, Sai; Castelli, Lydia M.; Hautbergue, Guillaume M.; Azzouz, Mimoun; Gordon, David E.; Krogan, Nevan J.; Ferraiuolo, Laura; Snyder, M; Shaw, Pamela J.; Rehwinkel, Jan; Cooper‐Knock, Johnathan

doi:10.26508/lsa.202201449

Cited by 3 publications

(4 citation statements)

References 53 publications

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“…Coronary artery disease is a known risk factor for poor COVID-19 outcomes [ 130 ]. EXOSC2 —Low expression of EXOSC2 was found to protect against clinical COVID-19 and impedes SARS-CoV-2 replication [ 131 ]. Likewise, aggregating COVID-19 GWAS statistics revealed an association between increased expression of EXOSC2 and higher risk of clinical COVID-19 [ 131 ].…”

Section: Discussionmentioning

confidence: 99%

“… EXOSC2 —Low expression of EXOSC2 was found to protect against clinical COVID-19 and impedes SARS-CoV-2 replication [ 131 ]. Likewise, aggregating COVID-19 GWAS statistics revealed an association between increased expression of EXOSC2 and higher risk of clinical COVID-19 [ 131 ]. EXOSC2 is a component of the RNA exosome that LC-MS/MS analysis demonstrated an interaction between the SARS-CoV-2 RNA polymerase and the majority of human RNA exosome components [ 131 ].…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, aggregating COVID-19 GWAS statistics revealed an association between increased expression of EXOSC2 and higher risk of clinical COVID-19 [ 131 ]. EXOSC2 is a component of the RNA exosome that LC-MS/MS analysis demonstrated an interaction between the SARS-CoV-2 RNA polymerase and the majority of human RNA exosome components [ 131 ]. Additionally, EXOSC2 has been linked to sudden cardiac death [ 132 ] due to cardiac conduction abnormalities and arrhythmia from QTc prolongation.…”

Section: Discussionmentioning

confidence: 99%

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Literature-Based Discovery to Elucidate the Biological Links between Resistant Hypertension and COVID-19

Kartchner,

McCoy,

Dubey

et al. 2023

Biology

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Multiple studies have reported new or exacerbated persistent or resistant hypertension in patients previously infected with COVID-19. We used literature-based discovery to identify and prioritize multi-scalar explanatory biology that relates resistant hypertension to COVID-19. Cross-domain text mining of 33+ million PubMed articles within a comprehensive knowledge graph was performed using SemNet 2.0. Unsupervised rank aggregation determined which concepts were most relevant utilizing the normalized HeteSim score. A series of simulations identified concepts directly related to COVID-19 and resistant hypertension or connected via one of three renin–angiotensin–aldosterone system hub nodes (mineralocorticoid receptor, epithelial sodium channel, angiotensin I receptor). The top-ranking concepts relating COVID-19 to resistant hypertension included: cGMP-dependent protein kinase II, MAP3K1, haspin, ral guanine nucleotide exchange factor, N-(3-Oxododecanoyl)-L-homoserine lactone, aspartic endopeptidases, metabotropic glutamate receptors, choline-phosphate cytidylyltransferase, protein tyrosine phosphatase, tat genes, MAP3K10, uridine kinase, dicer enzyme, CMD1B, USP17L2, FLNA, exportin 5, somatotropin releasing hormone, beta-melanocyte stimulating hormone, pegylated leptin, beta-lipoprotein, corticotropin, growth hormone-releasing peptide 2, pro-opiomelanocortin, alpha-melanocyte stimulating hormone, prolactin, thyroid hormone, poly-beta-hydroxybutyrate depolymerase, CR 1392, BCR-ABL fusion gene, high density lipoprotein sphingomyelin, pregnancy-associated murine protein 1, recQ4 helicase, immunoglobulin heavy chain variable domain, aglycotransferrin, host cell factor C1, ATP6V0D1, imipramine demethylase, TRIM40, H3C2 gene, COL1A1+COL1A2 gene, QARS gene, VPS54, TPM2, MPST, EXOSC2, ribosomal protein S10, TAP-144, gonadotropins, human gonadotropin releasing hormone 1, beta-lipotropin, octreotide, salmon calcitonin, des-n-octanoyl ghrelin, liraglutide, gastrins. Concepts were mapped to six physiological themes: altered endocrine function, 23.1%; inflammation or cytokine storm, 21.3%; lipid metabolism and atherosclerosis, 17.6%; sympathetic input to blood pressure regulation, 16.7%; altered entry of COVID-19 virus, 14.8%; and unknown, 6.5%.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Literature-Based Discovery to Elucidate the Biological Links between Resistant Hypertension and COVID-19

Kartchner,

McCoy,

Dubey

et al. 2023

Biology

View full text Add to dashboard Cite

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“…Synaptophysin (Cell Signaling #5461 (Wu et al, 2018)), NeuN (Cell Signaling #24307 (Tang et al, 2021)), PSD-95 (post-synaptic marker, Cell Signaling #36233 (Shui et al, 2022)), Homer-1 (post-synaptic marker, SC-136358 (Wang et al, 2014) (Tang et al, 2019)), mTOR S2448 (Cell signaling #2971 (Luo et al, 2022)), total mTOR (Cell signaling #2972 (Luo et al, 2022)), Akt T308 (Cell signaling #9275 (Mathieu et al, 2019)), Akt S473 (Cell signaling #4058 (Marko et al, 2020)), and total Akt (Cell signaling #4685 (Marko et al, 2020)) were measured as markers of insulin signaling. Ponceau S, α-tubulin (Cell signaling #2144 (Mertins et al, 2021)), GAPDH (Abcam ab8245 (Luo et al, 2023)) or β-Actin (Abcam ab8227 (Moll et al, 2023)) were utilized as loading controls.…”

Section: Western Blottingmentioning

confidence: 99%

Influence of metabolic stress and metformin on synaptic protein profile in SH‐SY5Y‐derived neurons

Yang,

Mohammad,

Finch

et al. 2023

Physiological Reports

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Insulin resistance (IR) is associated with reductions in neuronal proteins often observed with Alzheimer's disease (AD), however, the mechanisms through which IR promotes neurodegeneration/AD pathogenesis are poorly understood. Metformin (MET), a potent activator of the metabolic regulator AMPK is used to treat IR but its effectiveness for AD is unclear. We have previously shown that chronic AMPK activation impairs neurite growth and protein synthesis in SH‐SY5Y neurons, however, AMPK activation in IR was not explored. Therefore, we examined the effects of MET‐driven AMPK activation with and without IR. Retinoic acid‐differentiated SH‐SY5Y neurons were treated with: (1) Ctl: 24 h vehicle followed by 24 h Vehicle; (2) HI: 100 nM insulin (24 h HI followed by 24 h HI); or (3) MET: 24 h vehicle followed by 24 h 2 mM metformin; (4) HI/MET: 24 h 100 nM insulin followed by 24 h 100 nM INS+2 mM MET. INS and INS/MET groups saw impairments in markers of insulin signaling (Akt S473, mTOR S2448, p70s6k T389, and IRS‐1S636) demonstrating IR was not recovered with MET treatment. All treatment groups showed reductions in neuronal markers (post‐synaptic marker HOMER1 mRNA content and synapse marker synaptophysin protein content). INS and MET treatments showed a reduction in the content of the mature neuronal marker NeuN that was prevented by INS/MET. Similarly, increases in cell size/area, neurite length/area observed with INS and MET, were prevented with INS/MET. These findings indicate that IR and MET impair neuronal markers through distinct pathways and suggest that MET is ineffective in treating IR‐driven impairments in neurons.

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Molecular Biomarker Identification Using a Network-Based Bioinformatics Approach That Links COVID-19 With Smoking

Rahman

Amin

Yeasmin

et al. 2023

Bioinform Biol Insights

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The COVID-19 coronavirus, which primarily affects the lungs, is the source of the disease known as SARS-CoV-2. According to “Smoking and COVID-19: a scoping review,” about 32% of smokers had a severe case of COVID-19 pneumonia at their admission time and 15% of non-smokers had this case of COVID-19 pneumonia. We were able to determine which genes were expressed differently in each group by comparing the expression of gene transcriptomic datasets of COVID-19 patients, smokers, and healthy controls. In all, 37 dysregulated genes are common in COVID-19 patients and smokers, according to our analysis. We have applied all important methods namely protein-protein interaction, hub-protein interaction, drug-protein interaction, tf-gene interaction, and gene-MiRNA interaction of bioinformatics to analyze to understand deeply the connection between both smoking and COVID-19 severity. We have also analyzed Pathways and Gene Ontology where 5 significant signaling pathways were validated with previous literature. Also, we verified 7 hub-proteins, and finally, we validated a total of 7 drugs with the previous study.

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Low expression of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication

Cited by 3 publications

References 53 publications

Literature-Based Discovery to Elucidate the Biological Links between Resistant Hypertension and COVID-19

Literature-Based Discovery to Elucidate the Biological Links between Resistant Hypertension and COVID-19

Influence of metabolic stress and metformin on synaptic protein profile in SH‐SY5Y‐derived neurons

Molecular Biomarker Identification Using a Network-Based Bioinformatics Approach That Links COVID-19 With Smoking

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