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Mol Cell ; 81(13): 2838-2850.e6, 2021 07 01.
Статья в английский | MEDLINE | ID: covidwho-1202181

Реферат

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.


Тема - темы
Autoantigens/genetics , COVID-19/genetics , RNA, Viral/genetics , Ribonucleoproteins/genetics , SARS-CoV-2/genetics , COVID-19/virology , Coronavirus OC43, Human/genetics , Coronavirus OC43, Human/pathogenicity , HEK293 Cells , Host-Pathogen Interactions/genetics , Humans , Protein Binding/genetics , Protein Interaction Maps/genetics , RNA-Binding Proteins/genetics , SARS-CoV-2/pathogenicity , TOR Serine-Threonine Kinases/genetics , Transcription Factors/genetics , Transcriptome/genetics , Tripartite Motif Proteins/genetics , Ubiquitin-Protein Ligases/genetics , Virus Replication/genetics
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