Ribosomal RNA methylation by GidB is a capacitor for discrimination of mischarged tRNA

Despite redundant cellular pathways to minimize translational errors, errors in protein synthesis are common. Pathways and mechanisms to minimize errors are classified as pre-ribosomal or ribosomal. Pre-ribosomal pathways are primarily concerned with appropriate pairing of tRNAs with their cognate amino acid, whereas to date, ribosomal proof-reading has been thought to only be concerned with minimizing decoding errors, since it has been assumed that the ribosomal decoding centre is blind to mischarged tRNAs. Here, we identified that in mycobacteria, deletion of the 16S ribosomal RNA methyltransferase gidB led to increased discrimination of mischarged tRNAs. GidB deletion was necessary but not sufficient for reducing mistranslation due to misacylation. Discrimination only occurred in mycobacteria enriched from environments or genetic backgrounds with high rates of mistranslation. Our data suggest that mycobacterial ribosomes are capable of discriminating mischarged tRNAs and that 16S rRNA methylation by GidB may act as a capacitor for moderating translational error.