Scholarlink

<p>Coronaviruses genomes are enriched in suboptimal A- and U-ending codons, which are typically associated with reduced translation efficiency due to limited cognate tRNA availability. How coronavirus efficiently express their proteins despite this limitation remains unclear. By analyzing their codon usage, we identify four tRNA modifications—inosine (I), queuosine (Q), 5-methylcarboxymethyluridine/ 5-methylcarboxymethyl-2-thiouridine (mcm<sup>5</sup>U/mcm<sup>5</sup>s<sup>2</sup>U), and 5-methylcytidine/ 5-formylcytidine (m<sup>5</sup>C/f<sup>5</sup>C)—as essential for decoding their suboptimal codons. Notably, SARS-CoV-2 and HCoV-OC43 infections, representing severe and mild human infections, respectively, reprogram these modifications to favor viral protein synthesis. Mechanistically, this reprogramming was driven by altered expression of the corresponding tRNA modifying enzymes. Since both viruses induced DNA damage and oxidative stress—known to similarly alter&#xa0;Q, mcm<sup>5</sup>U/mcm<sup>5</sup>s<sup>2</sup>U, and m<sup>5</sup>C/f<sup>5</sup>C modifications to favor expression of stress response proteins—our findings support that coronavirus genomes have adapted to the tRNA modification landscape under stress conditions. Overall, coronaviruses orchestrate a codon-specific reprogramming of the host tRNA modification landscape, highlighting a conserved strategy that optimizes translation efficiency and represents a promising target for pan-coronavirus antiviral therapy development.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Coronaviruses reprogram the tRNA epitranscriptome to favor viral protein expression

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月19日

查看全文
  • Elena Muscolino,
  • Mireia Puig-Torrents,
  • Jaime Buigues Bisquert,
  • Diogo Correa Mendonca,
  • Marc Talló-Parra,
  • Gemma Perez-Vilaro,
  • Omar Caño-Prades,
  • Gavin R. Meehan,
  • Karen Kerr,
  • Vanessa Herder,
  • Miguel Chillón,
  • Alfredo Castello,
  • Rafael Sanjuan,
  • Arvind H. Patel,
  • Juana Díez

摘要

Coronaviruses genomes are enriched in suboptimal A- and U-ending codons, which are typically associated with reduced translation efficiency due to limited cognate tRNA availability. How coronavirus efficiently express their proteins despite this limitation remains unclear. By analyzing their codon usage, we identify four tRNA modifications—inosine (I), queuosine (Q), 5-methylcarboxymethyluridine/ 5-methylcarboxymethyl-2-thiouridine (mcm5U/mcm5s2U), and 5-methylcytidine/ 5-formylcytidine (m5C/f5C)—as essential for decoding their suboptimal codons. Notably, SARS-CoV-2 and HCoV-OC43 infections, representing severe and mild human infections, respectively, reprogram these modifications to favor viral protein synthesis. Mechanistically, this reprogramming was driven by altered expression of the corresponding tRNA modifying enzymes. Since both viruses induced DNA damage and oxidative stress—known to similarly alter Q, mcm5U/mcm5s2U, and m5C/f5C modifications to favor expression of stress response proteins—our findings support that coronavirus genomes have adapted to the tRNA modification landscape under stress conditions. Overall, coronaviruses orchestrate a codon-specific reprogramming of the host tRNA modification landscape, highlighting a conserved strategy that optimizes translation efficiency and represents a promising target for pan-coronavirus antiviral therapy development.