The Landscape of Aminoacyl-tRNA Synthetases Involved in Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Yajuan Feng; Kang Tang; Qi Lai; Jingxian Liang; Min Feng; Zhong-Wei Zhou; Haissi Cui; Xiangjun Du; Han Zhang; Litao Sun

doi:10.3389/fphys.2021.818297

The Landscape of Aminoacyl-tRNA Synthetases Involved in Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Front Physiol. 2022 Jan 26:12:818297. doi: 10.3389/fphys.2021.818297. eCollection 2021.

Authors

Yajuan Feng¹, Kang Tang¹, Qi Lai¹, Jingxian Liang¹, Min Feng², Zhong-Wei Zhou³, Haissi Cui⁴, Xiangjun Du¹, Han Zhang², Litao Sun¹

Affiliations

¹ School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
² Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
³ School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
⁴ Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, United States.

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.

Keywords: SARS-CoV-2; aminoacyl-tRNA synthetase; coronavirus; interaction network; the shortest path.