Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The SARS-CoV-2 RNA interactome.

ABSTRACT: SARS-CoV-2 is an RNA virus whose success as a pathogen relies on its abilities to repurpose host RNA-binding proteins (RBPs) and to evade antiviral RBPs. To uncover the SARS-CoV-2 RNA interactome, we here develop a robust ribonucleoprotein (RNP) capture protocol and identify 109 host factors that directly bind to SARS-CoV-2 RNAs. Applying RNP capture on another coronavirus, HCoV-OC43, revealed evolutionarily conserved interactions between coronaviral RNAs and host proteins. Transcriptome analyses and knockdown experiments delineated 17 antiviral RBPs, including ZC3HAV1, TRIM25, PARP12, and SHFL, and 8 proviral RBPs, such as EIF3D and CSDE1, which are responsible for co-opting multiple steps of the mRNA life cycle. This also led to the identification of LARP1, a downstream target of the mTOR signaling pathway, as an antiviral host factor that interacts with the SARS-CoV-2 RNAs. Overall, this study provides a comprehensive list of RBPs regulating coronaviral replication and opens new avenues for therapeutic interventions.

SUBMITTER: Lee S

PROVIDER: S-EPMC8075806 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The SARS-CoV-2 RNA interactome.

Lee Sungyul S Lee Young-Suk YS Choi Yeon Y Son Ahyeon A Park Youngran Y Lee Kyung-Min KM Kim Jeesoo J Kim Jong-Seo JS Kim V Narry VN

Molecular cell 20210427 13

SARS-CoV-2 is an RNA virus whose success as a pathogen relies on its abilities to repurpose host RNA-binding proteins (RBPs) and to evade antiviral RBPs. To uncover the SARS-CoV-2 RNA interactome, we here develop a robust ribonucleoprotein (RNP) capture protocol and identify 109 host factors that directly bind to SARS-CoV-2 RNAs. Applying RNP capture on another coronavirus, HCoV-OC43, revealed evolutionarily conserved interactions between coronaviral RNAs and host proteins. Transcriptome analyse ...[more]

PMID: 33989516

Similar Datasets

The Short- and Long-Range RNA-RNA Interactome of SARS-CoV-2.

Project description:The Coronaviridae is a family of positive-strand RNA viruses that includes SARS-CoV-2, the etiologic agent of the COVID-19 pandemic. Bearing the largest single-stranded RNA genomes in nature, coronaviruses are critically dependent on long-distance RNA-RNA interactions to regulate the viral transcription and replication pathways. Here we experimentally mapped the in vivo RNA-RNA interactome of the full-length SARS-CoV-2 genome and subgenomic mRNAs. We uncovered a network of RNA-RNA interactions spanning tens of thousands of nucleotides. These interactions reveal that the viral genome and subgenomes adopt alternative topologies inside cells and engage in different interactions with host RNAs. Notably, we discovered a long-range RNA-RNA interaction, the FSE-arch, that encircles the programmed ribosomal frameshifting element. The FSE-arch is conserved in the related MERS-CoV and is under purifying selection. Our findings illuminate RNA structure-based mechanisms governing replication, discontinuous transcription, and translation of coronaviruses and will aid future efforts to develop antiviral strategies.

| S-EPMC7643667 | biostudies-literature

Characterization and functional interrogation of the SARS-CoV-2 RNA interactome.

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic, which has led to a devastating global health crisis. The emergence of variants that escape neutralizing responses emphasizes the urgent need to deepen our understanding of SARS-CoV-2 biology. Using a comprehensive identification of RNA-binding proteins (RBPs) by mass spectrometry (ChIRP-MS) approach, we identify 107 high-confidence cellular factors that interact with the SARS-CoV-2 genome during infection. By systematically knocking down their expression in human lung epithelial cells, we find that the majority of the identified RBPs are SARS-CoV-2 proviral factors. In particular, we show that HNRNPA2B1, ILF3, QKI, and SFPQ interact with the SARS-CoV-2 genome and promote viral RNA amplification. Our study provides valuable resources for future investigations into the mechanisms of SARS-CoV-2 replication and the identification of host-centered antiviral therapies.

| S-EPMC9040432 | biostudies-literature

The SARS-CoV-2 RNA-protein interactome in infected human cells.

Project description:Characterizing the interactions that SARS-CoV-2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. Using RNA antisense purification and mass spectrometry, we identified up to 104 human proteins that directly and specifically bind to SARS-CoV-2 RNAs in infected human cells. We integrated the SARS-CoV-2 RNA interactome with changes in proteome abundance induced by viral infection and linked interactome proteins to cellular pathways relevant to SARS-CoV-2 infections. We demonstrated by genetic perturbation that cellular nucleic acid-binding protein (CNBP) and La-related protein 1 (LARP1), two of the most strongly enriched viral RNA binders, restrict SARS-CoV-2 replication in infected cells and provide a global map of their direct RNA contact sites. Pharmacological inhibition of three other RNA interactome members, PPIA, ATP1A1, and the ARP2/3 complex, reduced viral replication in two human cell lines. The identification of host dependency factors and defence strategies as presented in this work will improve the design of targeted therapeutics against SARS-CoV-2.

| S-EPMC7906908 | biostudies-literature

The SARS-CoV-2 RNA-protein interactome in infected human cells

Project description:Characterizing the interactions that SARS-CoV-2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. Using RNA antisense purification and mass spectrometry (RAP-MS), we identify up to 104 human proteins that directly and specifically bind to SARS-CoV-2 RNAs in infected human cells. We integrate the SARS-CoV-2 RNA interactome with proteome abundance changes induced by viral infection and link interactome proteins to cellular pathways relevant to SARS-CoV-2 infections. We demonstrate by genetic perturbation that CNBP and LARP1, two of the most strongly enriched viral RNA binders, restrict SARS-CoV-2 replication in infected cells and provide a global map of their direct RNA contact sites. Pharmacological inhibition of three other RNA interactome members, PPIA, ATP1A1, and the ARP2/3 complex, reduces viral replication in two human cell lines. The identification of host dependency factors and defence strategies as presented in this work will improve the design of targeted therapeutics against SARS-CoV-2.

2020-12-01 | GSE154430 | GEO

The short- and long-range RNA Interactome of SARS-CoV-2

Project description:The Coronaviridae are a family of positive- strand RNA viruses that includes SARS-CoV-2, the etiologic agent of the COVID-19 pandemic. Bearing the largest single stranded RNA genome in nature, coronaviruses are critically dependent on long-distance RNA-RNA interactions to regulate the viral transcription and replication pathways. Here we experimentally mapped the in vivo long-range RNA interactome of the full-length SARS-CoV-2 genome and the subgenomic mRNAs. We uncover a network of RNA-RNA interactions spanning tens of thousands of nucleotides that facilitate the unique transcription mode of coronaviruses, and reveal that the viral genome adopts alternative topologies inside cells and undergoes genome cyclization. Moreover, we discover long RNA-bridges between adjacent open reading frames that encircle the programmed ribosomal frame-shifting element, and demonstrate their conservation in vivo for the related MERS-CoV. Finally, the SARS-CoV-2 genome and subgenomic mRNAs engage in different sets of interactions with cellular RNAs. Our findings illuminate RNA-based mechanisms governing replication, discontinuous transcription, and translation of coronaviruses, and will aid future efforts to develop antiviral strategies.

2020-10-21 | GSE154662 | GEO

Global mapping of the SARS-CoV-2 microRNA interactome

Project description:Using the CLEAR-CLIP methodology (PMID: 26602609) combined with high throughput sequencing, all the binding sites of the Argonaute (AGO) proteins on SARS-CoV-2 RNAs were identified as well as the miRNAs contributing to each binding site. Consequently, SARS-CoV-2 mutants were engineered to investigate the functional relevance of the main binding sites. The effect of the infection on the cellular miRNAs was also investigated using the same CLEAR-CLIP data and RNA-Seq analysis.

2023-03-03 | GSE201894 | GEO

A computational map of the human-SARS-CoV-2 protein-RNA interactome predicted at single-nucleotide resolution.

Project description:RNA-binding proteins (RBPs) are critical host factors for viral infection, however, large scale experimental investigation of the binding landscape of human RBPs to viral RNAs is costly and further complicated due to sequence variation between viral strains. To fill this gap, we investigated the role of RBPs in the context of SARS-CoV-2 by constructing the first in silico map of human RBP-viral RNA interactions at nucleotide-resolution using two deep learning methods (pysster and DeepRiPe) trained on data from CLIP-seq experiments on more than 100 human RBPs. We evaluated conservation of RBP binding between six other human pathogenic coronaviruses and identified sites of conserved and differential binding in the UTRs of SARS-CoV-1, SARS-CoV-2 and MERS. We scored the impact of mutations from 11 variants of concern on protein-RNA interaction, identifying a set of gain- and loss-of-binding events, as well as predicted the regulatory impact of putative future mutations. Lastly, we linked RBPs to functional, OMICs and COVID-19 patient data from other studies, and identified MBNL1, FTO and FXR2 RBPs as potential clinical biomarkers. Our results contribute towards a deeper understanding of how viruses hijack host cellular pathways and open new avenues for therapeutic intervention.

| S-EPMC9940458 | biostudies-literature

Profile of the SARS-CoV-2 RNA interactome

Project description:SARS-CoV-2 is an RNA virus whose success as a pathogen relies on its ability to repurpose host RNA-binding proteins (RBPs) to form its own RNA interactome. Here, we developed and applied a robust ribonucleoprotein capture protocol to uncover the SARS-CoV-2 RNA interactome. We report 109 host factors that directly bind to SARS-CoV-2 RNAs including general antiviral factors such as ZC3HAV1, TRIM25, and PARP12. Applying RNP capture on another coronavirus HCoV-OC43 revealed evolutionarily conserved interactions between viral RNAs and host proteins. Network and transcriptome analyses delineated antiviral RBPs stimulated by JAK-STAT signaling and proviral RBPs responsible for hijacking multiple steps of the mRNA life cycle. By knockdown experiments, we further found that these viral-RNA-interacting RBPs act against or in favor of SARS-CoV-2. Overall, this study provides a comprehensive list of RBPs regulating coronaviral replication and opens new avenues for therapeutic interventions.

2021-04-28 | PXD024808 | Pride

Structures from "Engineering Neutralizing SARS-CoV Antibodies to Bind SARS-CoV-2"

Project description: Not available

| S-BSST379 | biostudies-other

A BioID-Derived Proximity Interactome for SARS-CoV-2 Proteins.

Project description:The novel coronavirus SARS-CoV-2 is responsible for the ongoing COVID-19 pandemic and has caused a major health and economic burden worldwide. Understanding how SARS-CoV-2 viral proteins behave in host cells can reveal underlying mechanisms of pathogenesis and assist in development of antiviral therapies. Here, the cellular impact of expressing SARS-CoV-2 viral proteins was studied by global proteomic analysis, and proximity biotinylation (BioID) was used to map the SARS-CoV-2 virus-host interactome in human lung cancer-derived cells. Functional enrichment analyses revealed previously reported and unreported cellular pathways that are associated with SARS-CoV-2 proteins. We have established a website to host the proteomic data to allow for public access and continued analysis of host-viral protein associations and whole-cell proteomes of cells expressing the viral-BioID fusion proteins. Furthermore, we identified 66 high-confidence interactions by comparing this study with previous reports, providing a strong foundation for future follow-up studies. Finally, we cross-referenced candidate interactors with the CLUE drug library to identify potential therapeutics for drug-repurposing efforts. Collectively, these studies provide a valuable resource to uncover novel SARS-CoV-2 biology and inform development of antivirals.

| S-EPMC8951556 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data