Scholarlink

<p>Modifications in the anticodon region of transfer RNA (tRNA) are essential for accurate and efficient protein synthesis. 5-Methyl-2-thiouridine derivatives (xm<sup>5</sup>s<sup>2</sup>U) are major modifications at the wobble position of tRNA anticodons decoding purine-ending two-codon sets. Although the thiocarbonyl group of xm<sup>5</sup>s<sup>2</sup>U enhances decoding efficiency, it is chemically susceptible to oxidative desulfuration, yielding 4-pyrimidinone derivatives (xm<sup>5</sup>h<sup>2</sup>U). Here, we identify xm<sup>5</sup>h<sup>2</sup>U derivatives in human cells and mouse tissues and confirm their cellular formation by spike-in experiments. Desulfurized tRNAs carrying 5-methoxycarbonylmethyl-4-pyrimidinone (mcm<sup>5</sup>h<sup>2</sup>U) show impaired codon recognition in a human reconstituted in vitro translation system. The mcm<sup>5</sup>h<sup>2</sup>U modification reduces aminoacylation of tRNAs for lysine, glutamate, and glutamine, but not arginine. Cryogenic electron microscopy reveals the structural basis of altered AAA/AAG decoding by mcm<sup>5</sup>h<sup>2</sup>U at the ribosomal A-site. These findings reveal a mechanism by which oxidative desulfuration of tRNA modifications dynamically regulates codon recognition and protein synthesis under oxidative stress conditions in human and mammalian cells.</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

Translational regulation by oxidative desulfuration of tRNA modifications

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月10日

查看全文
  • Yufeng Mo,
  • Kensuke Ishiguro,
  • Kenjyo Miyauchi,
  • Yuriko Sakaguchi,
  • Yosei Hanzawa,
  • Naho Akiyama,
  • Ayaka Murayama,
  • Kodai Machida,
  • Hiroaki Imataka,
  • Akio Yamashita,
  • Takayuki Ohira,
  • Mikako Shirouzu,
  • Tsutomu Suzuki

摘要

Modifications in the anticodon region of transfer RNA (tRNA) are essential for accurate and efficient protein synthesis. 5-Methyl-2-thiouridine derivatives (xm5s2U) are major modifications at the wobble position of tRNA anticodons decoding purine-ending two-codon sets. Although the thiocarbonyl group of xm5s2U enhances decoding efficiency, it is chemically susceptible to oxidative desulfuration, yielding 4-pyrimidinone derivatives (xm5h2U). Here, we identify xm5h2U derivatives in human cells and mouse tissues and confirm their cellular formation by spike-in experiments. Desulfurized tRNAs carrying 5-methoxycarbonylmethyl-4-pyrimidinone (mcm5h2U) show impaired codon recognition in a human reconstituted in vitro translation system. The mcm5h2U modification reduces aminoacylation of tRNAs for lysine, glutamate, and glutamine, but not arginine. Cryogenic electron microscopy reveals the structural basis of altered AAA/AAG decoding by mcm5h2U at the ribosomal A-site. These findings reveal a mechanism by which oxidative desulfuration of tRNA modifications dynamically regulates codon recognition and protein synthesis under oxidative stress conditions in human and mammalian cells.