Coronaviruses remodel the mature human tRNAome to modulate infection

TL;DR

Human coronaviruses change the tRNAome to help infection, with different viruses responding uniquely to tRNA and amino acid changes.

Contribution

This study reveals how coronaviruses remodel the mature human tRNAome to modulate infection, highlighting virus-specific dependencies on tRNA and amino acid availability.

Findings

Human coronaviruses upregulate the global tRNAome landscape in host cells.

Deprivation of asparagine or specific tRNA synthetase inhibits coronavirus 229E infection more than NL63 or SARS-CoV-2.

tRNA-Asn-AUU plays a prominent role in translational decoding of human coronaviruses.

Abstract

Current research on virus-host interactions primarily focuses on the transcription and translation of viral and host genes. However, there is a major knowledge gap between transcription and translation, known as translational decoding mediated by mature transfer RNAs (tRNAs) charged with amino acids. Codon usage analysis of seven human coronaviruses indicates that they are highly dissimilar from the human host. Quantification of the human tRNAome, consisting of 57 species, demonstrated that infections with these coronaviruses robustly upregulate the global tRNAome landscapes in host cells. Deprivation of individual amino acids or knockdown of TRNT1, the enzyme adding 3’-ACC terminal for tRNA aminoacylation, inhibited coronavirus infection. Integrative analysis of codon usage and the tRNAome landscape identified a prominent role of tRNA-Asn-AUU in translational decoding of different human coronaviruses. Deprivation of asparagine (Asn) or knockdown of Asparaginyl-tRNA Synthetase 1, an enzyme that charges the Asn amino acid onto tRNA-Asn acceptors, including tRNA-Asn-AUU, profoundly inhibited coronavirus 229E infection, but to a much lesser extent for NL63 and SARS-CoV-2. Collectively, we demonstrated that human coronaviruses are capable of remodeling the host mature tRNAome to facilitate infection. However, the regulatory patterns and sensitivities to interference, particularly at the single amino acid or tRNA levels, vary among different coronavirus species. These findings provide a new perspective for understanding virus-host interactions.

Figures