Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection

Kamel, Wael; Noerenberg, Marko; Cerikan, Berati; Chen, Honglin; Järvelin, Aino I; Kammoun, Mohamed; Lee, Young Seok; Ni, Shuai; García-Moreno, Manuel; Andrejeva, Anna; Deery, Michael J.; Johnson, Natasha; Neufeldt, Christopher J; Cortese, Mirko; Knight, Michael; Lilley, Kathryn S.; Martı́nez, Javier; Davis, Ilan; Bartenschlager, Ralf; Mohammed, Shabaz; Castelló, Alfredo

doi:10.1016/j.molcel.2021.05.023

Cited by 127 publications

(160 citation statements)

References 92 publications

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“…It is important to note that two stress granule proteins, G3BP1 and G3BP2, were most consistently identified in other studies [ 4 , 5 , 6 , 7 , 8 , 15 , 26 , 27 , 28 , 29 ]. G3BP1 and G3BP2 are downregulated during SARS-CoV-2 infection, and inhibition of stress granule formation by the N protein indicates that the N protein is involved in suppressing the host immune response to favour virus replication [ 5 , 30 ].…”

Section: Resultsmentioning

confidence: 99%

Interactome Analysis of the Nucleocapsid Protein of SARS-CoV-2 Virus

Zheng

Sun

et al. 2021

Pathogens

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SARS-CoV-2 infection has caused a global pandemic that has severely damaged both public health and the economy. The nucleocapsid protein of SARS-CoV-2 is multifunctional and plays an important role in ribonucleocapsid formation and viral genome replication. In order to elucidate its functions, interaction partners of the SARS-CoV-2 N protein in human cells were identified via affinity purification and mass spectrometry. We identified 160 cellular proteins as interaction partners of the SARS-CoV-2 N protein in HEK293T and/or Calu-3 cells. Functional analysis revealed strong enrichment for ribosome biogenesis and RNA-associated processes, including ribonucleoprotein complex biogenesis, ribosomal large and small subunits biogenesis, RNA binding, catalysis, translation and transcription. Proteins related to virus defence responses, including MOV10, EIF2AK2, TRIM25, G3BP1, ZC3HAV1 and ZCCHC3 were also identified in the N protein interactome. This study comprehensively profiled the viral–host interactome of the SARS-CoV-2 N protein in human cells, and the findings provide the basis for further studies on the pathogenesis and antiviral strategies for this emerging infection.

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Section: Resultsmentioning

confidence: 99%

Interactome Analysis of the Nucleocapsid Protein of SARS-CoV-2 Virus

Zheng

Sun

et al. 2021

Pathogens

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“…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 [178], and host mitochondria serve as an organelle platform for anti-SARS-CoV-2 immunity [179]. Approximately one-third of the cellular RNA-binding proteins (RBPs) are remodeled upon SARS-CoV-2 infection, and inhibition of these RBPs impairs SARS-CoV-2 infection [180].…”

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 viruses with positive-stranded RNA and 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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“…Transcriptomic analysis and RBP knockdown experiments further identified eight pro-viral RBPs and 17 anti-viral RBPs that regulate viral RNA replication [ 131 ]. A recent study by Kamel et al employed UV crosslinking-based comparative RNA interactome capture (cRIC) and viral RNA interactome capture (vRIC) to study cellular and viral proteins that are altered upon SARS-CoV-2 infection in epithelial human lung cancer cells (Calu-3) [ 132 ]. Similar to the observation from Flynn et al, this study also describes the lower efficiency but higher specificity of UV crosslinking compared to formaldehyde crosslinking.…”

Section: Introductionmentioning

confidence: 99%

“…This further explains why some proteins linked to viral RNA metabolism (within ORF1a/b) could not be identified by the vRIC approach used in this study. Their analysis revealed that SARS-CoV-2 remodels the cellular RNA-bound proteome (RBPome), including proteins that play a crucial role in viral life cycle, RNA metabolism, and anti-viral response [ 132 ]. The study identified 809 proteins enriched with RNA-binding domains, out of which 335 RBPs demonstrated a significant fold change at 24 h post infection [ 132 ].…”

Section: Introductionmentioning

confidence: 99%

“…Their analysis revealed that SARS-CoV-2 remodels the cellular RNA-bound proteome (RBPome), including proteins that play a crucial role in viral life cycle, RNA metabolism, and anti-viral response [ 132 ]. The study identified 809 proteins enriched with RNA-binding domains, out of which 335 RBPs demonstrated a significant fold change at 24 h post infection [ 132 ]. The study also illustrated the functional importance of the identified RBPs based on their prevalence in genome wide screens (RNA interference, CRISPR-Cas9, and haploid line screens) with 36 viruses from previous studies.…”

Section: Introductionmentioning

confidence: 99%

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Mutational Landscape and Interaction of SARS-CoV-2 with Host Cellular Components

et al. 2021

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The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid evolution has led to a global health crisis. Increasing mutations across the SARS-CoV-2 genome have severely impacted the development of effective therapeutics and vaccines to combat the virus. However, the new SARS-CoV-2 variants and their evolutionary characteristics are not fully understood. Host cellular components such as the ACE2 receptor, RNA-binding proteins (RBPs), microRNAs, small nuclear RNA (snRNA), 18s rRNA, and the 7SL RNA component of the signal recognition particle (SRP) interact with various structural and non-structural proteins of the SARS-CoV-2. Several of these viral proteins are currently being examined for designing antiviral therapeutics. In this review, we discuss current advances in our understanding of various host cellular components targeted by the virus during SARS-CoV-2 infection. We also summarize the mutations across the SARS-CoV-2 genome that directs the evolution of new viral strains. Considering coronaviruses are rapidly evolving in humans, this enables them to escape therapeutic therapies and vaccine-induced immunity. In order to understand the virus’s evolution, it is essential to study its mutational patterns and their impact on host cellular machinery. Finally, we present a comprehensive survey of currently available databases and tools to study viral–host interactions that stand as crucial resources for developing novel therapeutic strategies for combating SARS-CoV-2 infection.

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Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection

Cited by 127 publications

References 92 publications

Interactome Analysis of the Nucleocapsid Protein of SARS-CoV-2 Virus

Interactome Analysis of the Nucleocapsid Protein of SARS-CoV-2 Virus

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

Mutational Landscape and Interaction of SARS-CoV-2 with Host Cellular Components

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