Abstract
Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in translation by linking amino acids onto their cognate tRNAs during protein synthesis. During evolution, aaRSs develop numerous non-canonical functions that expand the roles of aaRSs in eukaryotic organisms. Although aaRSs have been implicated in viral infection, the function of aaRSs during infections with coronaviruses (CoVs) remains unclear. Here, we analyzed the data from transcriptomic and proteomic database on human cytoplasmic (cyto) and mitochondrial (mt) aaRSs across infections with three highly pathogenic human CoVs, with a particular focus on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found an overall downregulation of aaRSs at mRNA levels, while the protein levels of some mt-aaRSs and the phosphorylation of certain aaRSs were increased in response to SARS-CoV-2 infection. Strikingly, interaction network between SARS-CoV-2 and human aaRSs displayed a strong involvement of mt-aaRSs. Further co-immunoprecipitation (co-IP) experiments confirmed the physical interaction between SARS-CoV-2 M protein and TARS2. In addition, we identified the intermediate nodes and potential pathways involved in SARS-CoV-2 infection. This study provides an unbiased, overarching perspective on the correlation between aaRSs and SARS-CoV-2. More importantly, this work identifies TARS2, HARS2, and EARS2 as potential key factors involved in COVID-19.
Highlights
Aminoacyl-tRNA synthetases is an ancient enzyme family that links specific amino acids onto their cognate tRNAs
Despite well-documented function in protein synthesis, aaRSs, aaRS-interacting multi-functional proteins (AIMP) and the components of multi-synthetase complex (MSC) have recently been characterized as cellular sensors or immunoregulators in viral infections
EPRS1 can be released from the MSC and is involved in the anti-viral response of transmissible gastroenteritis coronavirus (TGEV), a coronavirus (CoV) that causes a life-threatening infection in pigs (Galan et al, 2009; Marquez-Jurado et al, 2015)
Summary
Aminoacyl-tRNA synthetases (aaRSs) is an ancient enzyme family that links specific amino acids onto their cognate tRNAs. The mammalian MSC contains nine cyto-aaRSs (EARS1, PARS1, IARS1, LARS1, MARS1, QARS1, KARS1, RARS1, and DARS1), and three non-enzymatic aaRS-interacting multi-functional proteins (AIMP), including aaRSs in SARS-CoV-2 Infection. Despite well-documented function in protein synthesis, aaRSs, AIMPs and the components of MSC have recently been characterized as cellular sensors or immunoregulators in viral infections. EPRS1 can be released from the MSC and is involved in the anti-viral response of transmissible gastroenteritis coronavirus (TGEV), a coronavirus (CoV) that causes a life-threatening infection in pigs (Galan et al, 2009; Marquez-Jurado et al, 2015). We found a strong involvement of aaRSs during viral infection process These viruses include human immunodeficiency virus 1 (HIV-1), influenza A virus, Zika virus, Ebola virus, etc. The systematical analysis of functional connection between human aaRSs and coronaviruses (CoVs), especially the current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is still missing
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