Selective regulation in ribosome biogenesis and protein production for efficient viral translation

Dong, Hui-Jun; Zhang, Rui; Yu, Kuang; Wang, Xiao‐Jia

doi:10.1007/s00203-020-02094-5

Cited by 27 publications

(18 citation statements)

References 141 publications

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“…Accordingly, 39.9% of these genes encode ribosomal proteins which are transcriptionally upregulated during viral infection to facilitate viral replication. 48 Various DEGs unique to this gene set include those encoding subunits of RNA polymerase II ( POLR2I , POLR2J , POLR2K , POLR2F , and POLR2L ), a host protein essential for transcription, and also demonstrated to be integral to replication of RNA viruses. 49 The nuclear transcribed mRNA catabolic process pathway (GO:0000956) consists of genes encoding proteins involved in the nonsense-mediated decay of transcripts carrying premature stop codons products.…”

Section: Resultsmentioning

confidence: 99%

RNA Sequencing of Lens Capsular Epithelium Implicates Novel Pathways in Pseudoexfoliation Syndrome

Mullany

Marshall

Zhou

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose Pseudoexfoliation syndrome (PEX) is a common systemic disease that results in severe and often irreversible vision loss. Despite considerable research effort, PEX remains incompletely understood. This study sought to perform the first RNAseq study in elucidate the pathophysiology of PEX, and contribute a publicly available transcriptomic data resource for future research. Methods Human ocular lens capsular epithelium samples were collected from 25 patients with PEX and 39 non-PEX controls undergoing cataract surgery. RNA extracted from these specimens was subjected to polyadenylated (mRNA) selection and deep bulk RNA sequencing. Differential expression analysis investigated protein-coding gene transcripts. Exploratory analyses used pathway analysis tools, and curated class- and disease-specific gene sets. Results Differential expression analysis demonstrated that 2882 genes were differentially expressed according to PEX status. Genes associated with viral gene expression pathways were among the most upregulated, alongside genes encoding ribosomal and mitochondrial respiratory transport chain proteins. Cell adhesion protein transcripts including type 4 collagen subunits were downregulated. Conclusions This comparative transcriptomic dataset highlights novel and previously recognized pathogenic pathways in PEX and provides the first comprehensive transcriptomic resource, adding an additional layer to build further understanding of PEX pathophysiology.

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Section: Resultsmentioning

confidence: 99%

RNA Sequencing of Lens Capsular Epithelium Implicates Novel Pathways in Pseudoexfoliation Syndrome

Mullany

Marshall

Zhou

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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“…Moreover, the minor region modulating the response to ToLCNDV in chromosome 2 of C. melo includes a Ribosomal protein L19 (MELO3C017364.2) remarkably affected by a high number of SNPs, upregulated at 6 and 12 dpi in PS. As viruses require host enzymes for translation ( Ignacio-Espinoza et al, 2020 ; Dong et al, 2021 ; Xiong et al, 2021 ), evolutionarily conserved genes involved in ribosome recruitment might be a plausible mechanism triggering the resistance response to ToLCNDV in melon.…”

Section: Discussionmentioning

confidence: 99%

RNA-Seq Transcriptome Analysis Provides Candidate Genes for Resistance to Tomato Leaf Curl New Delhi Virus in Melon

et al. 2022

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Tomato leaf curl New Delhi virus (ToLCNDV) emerged in the Mediterranean Basin in 2012 as the first DNA bipartite begomovirus (Geminiviridae family), causing severe yield and economic losses in cucurbit crops. A major resistance locus was identified in the wild melon accession WM-7 (Cucumis melo kachri group), but the mechanisms involved in the resistant response remained unknown. In this work, we used RNA-sequencing to identify disease-associated genes that are differentially expressed in the course of ToLCNDV infection and could contribute to resistance. Transcriptomes of the resistant WM-7 genotype and the susceptible cultivar Piñonet Piel de Sapo (PS) (C. melo ibericus group) in ToLCNDV and mock inoculated plants were compared at four time points during infection (0, 3, 6, and 12 days post inoculation). Different gene expression patterns were observed over time in the resistant and susceptible genotypes in comparison to their respective controls. Differentially expressed genes (DEGs) in ToLCNDV-infected plants were classified using gene ontology (GO) terms, and genes of the categories transcription, DNA replication, and helicase activity were downregulated in WM-7 but upregulated in PS, suggesting that reduced activity of these functions reduces ToLCNDV replication and intercellular spread and thereby contributes to resistance. DEGs involved in the jasmonic acid signaling pathway, photosynthesis, RNA silencing, transmembrane, and sugar transporters entail adverse consequences for systemic infection in the resistant genotype, and lead to susceptibility in PS. The expression levels of selected candidate genes were validated by qRT-PCR to corroborate their differential expression upon ToLCNDV infection in resistant and susceptible melon. Furthermore, single nucleotide polymorphism (SNPs) with an effect on structural functionality of DEGs linked to the main QTLs for ToLCNDV resistance have been identified. The obtained results pinpoint cellular functions and candidate genes that are differentially expressed in a resistant and susceptible melon line in response to ToLCNDV, an information of great relevance for breeding ToLCNDV-resistant melon cultivars.

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“…2 b). RPs have been reported to be hijacked by different viruses, including SARS-CoV-2, during infection to shut off host translation and facilitate IRES-mediated translation of viral proteins [51] , [52] , [53] . Inspection for reported interactions between shortlisted RPs with the SARS-CoV-2 proteins revealed that nsp1, nsp8, nsp9, and nucleocapsid (N) proteins of SARS-CoV-2 are potential interactors ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples

Biji

Khatun²,

Swaraj³

et al. 2021

EBioMedicine

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Background While our battle with the COVID-19 pandemic continues, a multitude of Omics data have been generated from patient samples in various studies. Translation of these data into clinical interventions against COVID-19 remains to be accomplished. Exploring host response to COVID-19 in the upper respiratory tract can unveil prognostic markers and therapeutic targets. Methods We conducted a meta-analysis of published transcriptome and proteome profiles of respiratory samples of COVID-19 patients to shortlist high confidence upregulated host factors. Subsequently, mRNA overexpression of selected genes was validated in nasal swabs from a cohort of COVID-19 positive/negative, symptomatic/asymptomatic individuals. Guided by this analysis, we sought to check for potential drug targets. An FDA-approved drug, Auranofin, was tested against SARS-CoV-2 replication in cell culture and Syrian hamster challenge model. Findings The meta-analysis and validation in the COVID-19 cohort revealed S100 family genes (S100A6, S100A8, S100A9, and S100P) as prognostic markers of severe COVID-19. Furthermore, Thioredoxin (TXN) was found to be consistently upregulated. Auranofin, which targets Thioredoxin reductase, was found to mitigate SARS-CoV-2 replication in vitro. Furthermore, oral administration of Auranofin in Syrian hamsters in therapeutic as well as prophylactic regimen reduced viral replication, IL-6 production, and inflammation in the lungs. Interpretation Elevated mRNA level of S100s in the nasal swabs indicate severe COVID-19 disease, and FDA-approved drug Auranofin mitigated SARS-CoV-2 replication in preclinical hamster model. Funding This study was supported by the DBT-IISc partnership program (DBT (IED/4/2020-MED/DBT)), the Infosys Young Investigator award (YI/2019/1106), DBT-BIRAC grant (BT/CS0007/CS/02/20) and the DBT-Wellcome Trust India Alliance Intermediate Fellowship (IA/I/18/1/503613) to ST lab.

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Selective regulation in ribosome biogenesis and protein production for efficient viral translation

Cited by 27 publications

References 141 publications

RNA Sequencing of Lens Capsular Epithelium Implicates Novel Pathways in Pseudoexfoliation Syndrome

RNA Sequencing of Lens Capsular Epithelium Implicates Novel Pathways in Pseudoexfoliation Syndrome

RNA-Seq Transcriptome Analysis Provides Candidate Genes for Resistance to Tomato Leaf Curl New Delhi Virus in Melon

Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples

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