Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

Flynn, Ryan A.; Belk, Julia A.; Qi, Yanyan; Yasumoto, Yuki; Jin, Wei; Alfajaro, Mia Madel; Shi, Quanming; Mumbach, Maxwell R.; Limaye, Aditi; DeWeirdt, Peter C; Schmitz, Cameron O.; Parker, Kevin R.; Woo, Elizabeth; Chang, Howard Y.; Horváth, Tamas L.; Carette, Jan E.; Bertozzi, Carolyn R.; Wilen, Craig B.; Satpathy, Ansuman T.

doi:10.1016/j.cell.2021.03.012

Cited by 173 publications

(221 citation statements)

References 78 publications

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“…RBPs are likely candidates for host factors involved in the response of human cells to SARS-CoV-2, as well as viral manipulation of host machinery. During preparation of this study, two experimental studies 85,86 reported hundreds of proteins that interact with SARS-CoV-2 RNA in human liver-derived cell lines. Encouragingly, they validated binding of several candidate proteins highlighted by our analysis (Table 2 and Supplementary Data 13).…”

Section: Discussionmentioning

confidence: 99%

“…Selected human RBPs whose putative binding sites are enriched in regions of the SARS-CoV-2 genome, along with experimental information. Log2 fold change is reported only for differentially expressed genes (DEGs) with FDR-adjusted p-value < 0.05. scRNA indicates whether the RBP is co-expressed with ACE2 and TMPRSS2 in single-cell RNA-seq data from human lung cells55 ; PPI Map indicates reported interaction with a SARS-CoV-2 viral protein18 ; viral RNA binding indicates RBPs experimentally found to interact with SARS-CoV-2 RNA in a human liver cell line85,86 . UTR untranslated region.…”

mentioning

confidence: 99%

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Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

Ferrarini

Rebollo

et al. 2021

Commun Biol

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The novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after emerging in Wuhan, China. Here we analyzed public host and viral RNA sequencing data to better understand how SARS-CoV-2 interacts with human respiratory cells. We identified genes, isoforms and transposable element families that are specifically altered in SARS-CoV-2-infected respiratory cells. Well-known immunoregulatory genes including CSF2, IL32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were upregulated. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and eukaryotic initiation factor 4 (eIF4b). We also identified a viral sequence variant with a statistically significant skew associated with age of infection, that may contribute to intracellular host–pathogen interactions. These findings can help identify host mechanisms that can be targeted by prophylactics and/or therapeutics to reduce the severity of COVID-19.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

Ferrarini

Rebollo

et al. 2021

Commun Biol

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“…1C, Supplementary Table 1). Proteins recently identified in genome-wide interactome studies as direct RNA interaction partners for SARS-CoV-2 were selected for downstream functional characterization 3,[20][21][22] . Several of these have been shown to play a role in RNA processing, including splicing (such as HNRNPs F, H1, and H2), RNA trimming (POP1) and RNA decay (ZAP) [23][24][25] .…”

Section: Sars-cov-2 Prf Rna Capture Identifies Novel Host Interactorsmentioning

confidence: 99%

Revealing the host antiviral protein ZAP-S as an inhibitor of SARS-CoV-2 programmed ribosomal frameshifting

Zimmer

Kibe

Rand

et al. 2021

Preprint

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Programmed ribosomal frameshifting (PRF) is a fundamental gene expression event in many viruses including SARS-CoV-2, which allows production of essential structural and replicative enzymes from an alternative reading frame. Despite the importance of PRF for the viral life cycle, it is still largely unknown how and to what extent cellular factors alter mechanical properties of frameshifting RNA molecules and thereby impact virulence. This prompted us to comprehensively dissect the interplay between the host proteome and the SARS-CoV-2 frameshift element. Here, we reveal that zinc-finger antiviral protein (ZAP-S) is a direct and specific regulator of PRF in SARS-CoV-2 infected cells. ZAP-S overexpression strongly impairs frameshifting and viral replication. Using in vitro ensemble and single-molecule techniques, we further demonstrate that ZAP-S directly interacts with the SARS-CoV-2 RNA and ribosomes and interferes with the folding of the frameshift RNA. Together these data illuminate ZAP-S as de novo host-encoded specific inhibitor of SARS-CoV-2 frameshifting and expand our understanding of RNA-based gene regulation.

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“…Proteomic studies further showed that SARS-CoV-2 reshapes cellular translation, splicing, carbon metabolism, protein homeostasis, and nucleic acid metabolism [143]. In addition to viral proteins, it was shown that SARS-CoV-2 RNA directly and specifically binds and/or modulates a broad network of human proteins in infected human cells [145], and host mitochondria serve as an organelle platform for anti-SARS-CoV-2 immunity [146].…”

Section: Virus-host Interaction and Exploitation Of The Cellular Machinerymentioning

confidence: 99%

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

Duerr¹,

Jimenez²,

Dittmann³

2021

Preprint

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SARS-CoV-2 and HIV are zoonotic viruses that rapidly reached pandemic scale causing global losses and fear. The COVID-19 and AIDS pandemics ignited massive efforts worldwide to develop antiviral strategies and characterize viral architectures, biological and immunological properties, and clinical outcomes. Although both viruses have a comparable appearance as enveloped, positive-stranded RNA viruses with envelope spikes mediating cellular entry, the entry process, downstream biological and immunological pathways, clinical outcomes, and disease courses are strikingly different. This review provides a systemic comparison of both viruses’ structural and functional characteristics delineating their distinct strategies for efficient spread.

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Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

Cited by 173 publications

References 78 publications

Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

Revealing the host antiviral protein ZAP-S as an inhibitor of SARS-CoV-2 programmed ribosomal frameshifting

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

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