Modifications in the T arm of tRNA globally determine tRNA maturation, function, and cellular fitness

• 成果类型: Article
• 署名作者: Schultz, Sarah K.; Katanski, Christopher D.; Halucha, Mateusz; Pena, Noah; Fahlman, Richard P.; Pan, Tao; Kothe, Ute
• 署名单位: University of Manitoba; University of Lethbridge; University of Chicago; University of Chicago; University of Alberta
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11860
• DOI: 10.1073/pnas.2401154121
• 发表日期: 2024-06-25
• 关键词: escherichia-coli; pseudouridine synthase; position 55; trub; genes; ACID

摘要

Almost all elongator tRNAs (Transfer RNAs) harbor 5 - methyluridine 54 and pseudouridine 55 in the T arm, generated by the enzymes TrmA and TruB, respectively, in Escherichia coli. TrmA and TruB both act as tRNA chaperones, and strains lacking trmA or truB are outcompeted by wild type. Here, we investigate how TrmA and TruB contribute to cellular fitness. Deletion of trmA and truB in E. coli causes a global decrease in aminoacylation and alters other tRNA modifications such as acp 3 U47. While overall protein synthesis is not affected in Delta trmA and Delta truB strains, the translation of a subset of codons is significantly impaired. As a consequence, we observe translationally reduced expression of many specific proteins, that are either encoded with a high frequency of these codons or that are large proteins. The resulting proteome changes are not related to a specific growth phenotype, but overall cellular fitness is impaired upon deleting trmA and truB in accordance with a general protein synthesis impact. In conclusion, we demonstrate that universal modifications of the tRNA T arm are critical for global tRNA function by enhancing tRNA maturation, tRNA aminoacylation, and translation, thereby improving cellular fitness irrespective of the growth conditions which explains the conservation of trmA and truB .