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Review
. 2023 Dec 20;51(6):2127-2141.
doi: 10.1042/BST20230527.

Aminoacyl-tRNA synthetase interactions in SARS-CoV-2 infection

Debjit Khan  1 , Paul L Fox  1
Affiliations
Review

Aminoacyl-tRNA synthetase interactions in SARS-CoV-2 infection

Debjit Khan et al. Biochem Soc Trans. .

Abstract

Aminoacyl-tRNA synthetases (aaRSs) are ancient enzymes that serve a foundational role in the efficient and accurate translation of genetic information from messenger RNA to proteins. These proteins play critical, non-canonical functions in a multitude of cellular processes. Multiple viruses are known to hijack the functions of aaRSs for proviral outcomes, while cells modify antiviral responses through non-canonical functions of certain synthetases. Recent findings have revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronaviral disease 19 (COVID-19), utilizes canonical and non-canonical functions of aaRSs, establishing a complex interplay of viral proteins, cellular factors and host aaRSs. In a striking example, an unconventional multi-aaRS complex consisting of glutamyl-prolyl-, lysyl-, arginyl- and methionyl-tRNA synthetases interact with a previously unknown RNA-element in the 3'-end of SARS-CoV-2 genomic and subgenomic RNAs. This review aims to highlight the aaRS-SARS-CoV-2 interactions identified to date, with possible implications for the biology of host aaRSs in SARS-CoV-2 infection.

Keywords: RNA virus; SARS-COV-2; UTR; aminoacyl-tRNA synthetase; post-transcriptional region.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1.
Figure 1.. Non-canonical functions of aminoacyl-tRNA synthetases.
Aminoacyl-tRNA synthetases are color-coded to highlight multiple functions of same protein. MSC-resident (italics), non-MSC cytoplasmic (plain font), and mitochondrial (outline font) synthetases are indicated.
Figure 2.
Figure 2.. An integrated model of SARS-CoV-2 ORF10, SPEAR element, and virus RNA cyclization [125].
RNAs are cyclized by base-pairing of the 3′-end genomic terminus immediately downstream of the SPEAR element, with 16 complementary nucleotides of the TRS-L (transcription regulatory sequence-L) or 21 nt of the 5′UTR [128]. The start codon lies 0–2 nt downstream of this base-paired region in most sgRNAs, except in N (8 nt) and M (44 nt); in gRNA, the ORF1a/b start codon lies further downstream, with intervening 5′UTR stem–loop structures (not shown). Cell activation by SARS-CoV-2 spike, IFN-γ, or insulin induces ORF10 translation and formation of the SPEAR element-binding TASRI (tetra-aminoacyl-tRNA synthetase sarbecoviral RNA-interacting) complex.
See this image and copyright information in PMC

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