Loss of N1-methylation of G37 in tRNA induces ribosome stalling and reprograms gene expression

N 1 -methylation of G37 is required for a subset of tRNAs to maintain the translational reading-frame. While loss of m 1 G37 increases ribosomal +1 frameshifting, whether it incurs additional translational defects is unknown. Here, we address this question by applying ribosome profiling to gain a ge...

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Bibliographic Details
Published in:eLife 2021-08, Vol.10
Main Authors: Masuda, Isao, Hwang, Jae-Yeon, Christian, Thomas, Maharjan, Sunita, Mohammad, Fuad, Gamper, Howard, Buskirk, Allen R, Hou, Ya-Ming
Format: Article
Language:English
Subjects:
Aminoacylation
Apoptosis
Binding sites
Biosynthesis
Codons
DNA methylation
E coli
Enzymes
Gene expression
Genomes
m1G37-tRNA
Microbiology and Infectious Disease
Peptides
Protein biosynthesis
Protein deficiency
Protein synthesis
Proteins
Reading
ribosome pausing
ribosome profling
Salmonella
Stringent response
Transfer RNA
Translation
TrmD
tRNA
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Summary:N 1 -methylation of G37 is required for a subset of tRNAs to maintain the translational reading-frame. While loss of m 1 G37 increases ribosomal +1 frameshifting, whether it incurs additional translational defects is unknown. Here, we address this question by applying ribosome profiling to gain a genome-wide view of the effects of m 1 G37 deficiency on protein synthesis. Using E coli as a model, we show that m 1 G37 deficiency induces ribosome stalling at codons that are normally translated by m 1 G37-containing tRNAs. Stalling occurs during decoding of affected codons at the ribosomal A site, indicating a distinct mechanism than that of +1 frameshifting, which occurs after the affected codons leave the A site. Enzyme- and cell-based assays show that m 1 G37 deficiency reduces tRNA aminoacylation and in some cases peptide-bond formation. We observe changes of gene expression in m 1 G37 deficiency similar to those in the stringent response that is typically induced by deficiency of amino acids. This work demonstrates a previously unrecognized function of m 1 G37 that emphasizes its role throughout the entire elongation cycle of protein synthesis, providing new insight into its essentiality for bacterial growth and survival.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.70619