Conserved 5-methyluridine tRNA modification modulates ribosome translocation

• 成果类型: Article
• 署名作者: Jones, Joshua D.; Franco, Monika K.; Giles, Rachel N.; Eyler, Daniel E.; Tardu, Mehmet; Smith, Tyler J.; Snyder, Laura R.; Polikanov, Yury S.; Kennedy, Robert T.; Niederer, Rachel O.; Koutmou, Kristin S.
• 署名单位: University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; University of Michigan System; University of Michigan
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12322
• DOI: 10.1073/pnas.2401743121
• 发表日期: 2024-08-27
• 关键词: ribonucleic-acid; structural basis; hygromycin-b; t-loop; methylation; site

摘要

While the centrality of posttranscriptional modifications to RNA biology has long been acknowledged, the function of the vast majority of modified sites remains to be discovered. Illustrative of this, there is not yet a discrete biological role assigned for one of the most highly conserved modifications, 5- methyluridine at position 54 in tRNAs (m5U54). Here, we uncover contributions of m5U54 to both tRNA maturation and protein synthesis. Our mass spectrometry analyses demonstrate that cells lacking the enzyme that installs m5U in the T- loop (TrmA in Escherichia coli, Trm2 in Saccharomyces cerevisiae) exhibit altered tRNA modification patterns. Furthermore, m5U54- deficient tRNAs are desensitized to small molecules that prevent translocation in vitro. This finding is consistent with our observations that relative to wild- type cells, trm2 Delta cell growth and transcriptome-wide gene expression are less perturbed by translocation inhibitors. Together our data suggest a model in which m5U54 acts as an important modulator of tRNA maturation and translocation of the ribosome during protein synthesis.