摘要
The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection is currently a global pandemic.Extensive investigations have been performed to study the clinical and cellular effects of SARS-CoV-2 infection.Mass spectrometry-based proteomics studies have revealed the cellular changes due to the infection and identified a plethora of interactors for all SARS-CoV-2 components,except for the longest non-structural protein 3(NSP3).Here,we expressed the full-length NSP3 proteins of SARS-CoV and SARS-CoV-2 to investigate their unique and shared functions using multi-omics methods.We conducted interactome,phosphoproteome,ubiquitylome,transcriptome,and proteome analyses of NSP3-expressing cells.We found that NSP3 plays essential roles in cellular functions such as RNA metabolism and immune response(e.g.,NF-κB signal transduction).Interestingly,we showed that SARS-CoV-2 NSP3 has both endoplasmic reticulum and mitochondrial localizations.In addition,SARS-CoV-2 NSP3 is more closely related to mitochondrial ribosomal proteins,whereas SARS-CoV NSP3 is related to the cytosolic ribosomal proteins.In summary,our integrative multi-omics study of NSP3 improves the understanding of the functions of NSP3 and offers potential targets for the development of anti-SARS strategies.
基金
supported by the Guangdong Science and Technology Project,China(Grant Nos.2018B030306047 and 2020B1212060052)
the National Natural Science Foundation of China(Grant Nos.31770889 and 31801180)
the Guangzhou Science and Technology Project,China(Grant No.201904010469)
the Guangzhou Regenerative Medicine and Health Guangdong Laboratory project,China(Grant No.2018GZR110104003)。
