tRNA methylation resolves codon usage bias at the limit of cell viability

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Codon usage bias correlates with tRNA isoacceptor abundance.
• The role of tRNA post-transcriptional modifications in resolving codon usage bias is largely unknown.
• N1-methylation of guanosine at position 37 (m1G37) is a key tRNA modification.

Purpose of the Study:

• To investigate how m1G37 resolves differential decoding of proline codons.
• To identify genetic factors involved in the interplay between m1G37 and tRNA function.
• To understand the impact of m1G37 on cell viability and proline translation.

Main Methods:

• Genome-wide suppressor screening in Escherichia coli lacking m1G37.
• Analysis of proS suppressor mutations.
• Characterization of tRNA prolyl-aminoacylation and translation in suppressor strains.

Main Results:

• m1G37 acts as a neutralizer for differential decoding of proline codons.
• Suppressor mutations decouple tRNA methylation from prolyl-aminoacylation, revealing m1G37's role.
• Lack of m1G37 necessitates a minor tRNA isoacceptor for cell viability.

Conclusions:

• m1G37 is essential for neutralizing differential translation of proline codons by the major isoacceptor.
• The absence of m1G37 impacts bacterial survival by altering tRNA decoding efficiency.
• This finding has implications for targeting bacterial species reliant on the major isoacceptor.