A tRNA modification in Mycobacterium tuberculosis facilitates optimal intracellular growth

Diverse chemical modifications fine-tune the function and metabolism of tRNA. Although tRNA modification is universal in all kingdoms of life, profiles of modifications, their functions, and physiological roles have not been elucidated in most organisms including the human pathogen, ( ), the causati...

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Published ineLife Vol. 12
Main Authors Tomasi, Francesca G, Kimura, Satoshi, Rubin, Eric J, Waldor, Matthew K
Format Journal Article
LanguageEnglish
Published England eLife Sciences Publications Ltd 27.09.2023
eLife Sciences Publications, Ltd
Subjects
Amino acids
Biochemistry and Chemical Biology
Biosynthesis
E coli
Enzymes
Genomes
Homology
Humans
Intracellular
Macrophages
Microbiology and Infectious Disease
Mycobacterium tuberculosis
Mycobacterium tuberculosis - genetics
Organisms
Pathogens
Proteins
Reverse transcription
Ribonucleic acid
RNA
RNA modification
RNA Processing, Post-Transcriptional
Transfer RNA
tRNA
tRNA Ala
tRNA sequencing
Tuberculosis
Uridine
RNA modification
Mycobacterium tuberculosis
chemical biology
tRNA
infectious disease
biochemistry
microbiology
tRNA sequencing
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Summary:Diverse chemical modifications fine-tune the function and metabolism of tRNA. Although tRNA modification is universal in all kingdoms of life, profiles of modifications, their functions, and physiological roles have not been elucidated in most organisms including the human pathogen, ( ), the causative agent of tuberculosis. To identify physiologically important modifications, we surveyed the tRNA of , using tRNA sequencing (tRNA-seq) and genome-mining. Homology searches identified 23 candidate tRNA modifying enzymes that are predicted to create 16 tRNA modifications across all tRNA species. Reverse transcription-derived error signatures in tRNA-seq predicted the sites and presence of nine modifications. Several chemical treatments prior to tRNA-seq expanded the number of predictable modifications. Deletion of genes encoding two modifying enzymes, TruB and MnmA, eliminated their respective tRNA modifications, validating the presence of modified sites in tRNA species. Furthermore, the absence of attenuated growth in macrophages, suggesting that MnmA-dependent tRNA uridine sulfation contributes to intracellular growth. Our results lay the foundation for unveiling the roles of tRNA modifications in pathogenesis and developing new therapeutics against tuberculosis.
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These authors contributed equally to this work.
Department of Microbiology and Immunology, Cornell University, Ithaca, United States.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.87146