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Coronaviruses reprogram the tRNA epitranscriptome to favor viral protein expression

Elena Muscolino1, Mireia Puig-Torrents1, Jaime Buigues Bisquert2

  • 1Molecular Virology group, Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain.

Nature Communications
|February 19, 2026
PubMed

Insights

Coronaviruses use specific tRNA modifications to efficiently translate their genomes, despite using suboptimal codons. Viral infections reprogram these modifications, offering a potential target for antiviral therapies.

Area of Science:

  • Molecular Biology
  • Virology
  • Genomics

Background:

  • Coronaviruses utilize suboptimal codons, potentially hindering protein synthesis due to limited tRNA availability.
  • The mechanism by which coronaviruses achieve efficient protein expression despite codon bias is not fully understood.

Purpose of the Study:

  • To investigate the role of tRNA modifications in coronavirus protein synthesis.
  • To identify specific tRNA modifications essential for decoding suboptimal codons used by coronaviruses.
  • To explore how viral infections, such as SARS-CoV-2 and HCoV-OC43, alter tRNA modifications.

Main Methods:

  • Analysis of coronavirus codon usage patterns.
  • Identification of key tRNA modifications (inosine, queuosine, mcm5U/mcm5s2U, m5C/f5C).
  • Investigation of tRNA modifying enzyme expression during viral infections.

Main Results:

  • Four specific tRNA modifications are crucial for decoding suboptimal viral codons.
  • SARS-CoV-2 and HCoV-OC43 infections reprogram these tRNA modifications to enhance viral protein synthesis.
  • Viral reprogramming of tRNA modifications is linked to altered expression of tRNA modifying enzymes.

Conclusions:

  • Coronaviruses adapt to the host tRNA modification landscape, particularly under stress conditions.
  • This codon-specific reprogramming optimizes viral translation efficiency.
  • Targeting tRNA modification pathways presents a potential strategy for pan-coronavirus antiviral development.

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