tetano
Editor, Senior Moderator
Mol Cell
. 2023 Dec 13:S1097-2765(23)00978-4.
doi: 10.1016/j.molcel.2023.11.032. Online ahead of print. SARS-CoV-2 RNA stabilizes host mRNAs to elicit immunopathogenesis
Hailian Zhao[SUP] 1 [/SUP], Zhaokui Cai[SUP] 2 [/SUP], Jian Rao[SUP] 3 [/SUP], Di Wu[SUP] 4 [/SUP], Lei Ji[SUP] 2 [/SUP], Rong Ye[SUP] 1 [/SUP], Di Wang[SUP] 1 [/SUP], Juan Chen[SUP] 2 [/SUP], Changchang Cao[SUP] 2 [/SUP], Naijing Hu[SUP] 1 [/SUP], Ting Shu[SUP] 4 [/SUP], Ping Zhu[SUP] 5 [/SUP], Jianwei Wang[SUP] 6 [/SUP], Xi Zhou[SUP] 7 [/SUP], Yuanchao Xue[SUP] 8 [/SUP]
Affiliations
SARS-CoV-2 RNA interacts with host factors to suppress interferon responses and simultaneously induces cytokine release to drive the development of severe coronavirus disease 2019 (COVID-19). However, how SARS-CoV-2 hijacks host RNAs to elicit such imbalanced immune responses remains elusive. Here, we analyzed SARS-CoV-2 RNA in situ structures and interactions in infected cells and patient lung samples using RIC-seq. We discovered that SARS-CoV-2 RNA forms 2,095 potential duplexes with the 3' UTRs of 205 host mRNAs to increase their stability by recruiting RNA-binding protein YBX3 in A549 cells. Disrupting the SARS-CoV-2-to-host RNA duplex or knocking down YBX3 decreased host mRNA stability and reduced viral replication. Among SARS-CoV-2-stabilized host targets, NFKBIZ was crucial for promoting cytokine production and reducing interferon responses, probably contributing to cytokine storm induction. Our study uncovers the crucial roles of RNA-RNA interactions in the immunopathogenesis of RNA viruses such as SARS-CoV-2 and provides valuable host targets for drug development.
Keywords: COVID-19; RIC-seq; RNA stability; RNA-RNA interaction; RNA-binding protein; SARS-CoV-2.
. 2023 Dec 13:S1097-2765(23)00978-4.
doi: 10.1016/j.molcel.2023.11.032. Online ahead of print. SARS-CoV-2 RNA stabilizes host mRNAs to elicit immunopathogenesis
Hailian Zhao[SUP] 1 [/SUP], Zhaokui Cai[SUP] 2 [/SUP], Jian Rao[SUP] 3 [/SUP], Di Wu[SUP] 4 [/SUP], Lei Ji[SUP] 2 [/SUP], Rong Ye[SUP] 1 [/SUP], Di Wang[SUP] 1 [/SUP], Juan Chen[SUP] 2 [/SUP], Changchang Cao[SUP] 2 [/SUP], Naijing Hu[SUP] 1 [/SUP], Ting Shu[SUP] 4 [/SUP], Ping Zhu[SUP] 5 [/SUP], Jianwei Wang[SUP] 6 [/SUP], Xi Zhou[SUP] 7 [/SUP], Yuanchao Xue[SUP] 8 [/SUP]
Affiliations
- PMID: 38128540
- DOI: 10.1016/j.molcel.2023.11.032
SARS-CoV-2 RNA interacts with host factors to suppress interferon responses and simultaneously induces cytokine release to drive the development of severe coronavirus disease 2019 (COVID-19). However, how SARS-CoV-2 hijacks host RNAs to elicit such imbalanced immune responses remains elusive. Here, we analyzed SARS-CoV-2 RNA in situ structures and interactions in infected cells and patient lung samples using RIC-seq. We discovered that SARS-CoV-2 RNA forms 2,095 potential duplexes with the 3' UTRs of 205 host mRNAs to increase their stability by recruiting RNA-binding protein YBX3 in A549 cells. Disrupting the SARS-CoV-2-to-host RNA duplex or knocking down YBX3 decreased host mRNA stability and reduced viral replication. Among SARS-CoV-2-stabilized host targets, NFKBIZ was crucial for promoting cytokine production and reducing interferon responses, probably contributing to cytokine storm induction. Our study uncovers the crucial roles of RNA-RNA interactions in the immunopathogenesis of RNA viruses such as SARS-CoV-2 and provides valuable host targets for drug development.
Keywords: COVID-19; RIC-seq; RNA stability; RNA-RNA interaction; RNA-binding protein; SARS-CoV-2.