Imbalance of tRNA~(Pro) isoacceptors induces +1 frameshifting at near-cognate codons

摘要

Increased expression of the CCU/CCA/CCG-decoding tRNA_3~(Pro) on a multicopy plasmid leads to suppression of several +1 frameshift mutations in Salmonella enterica serovar Typhimurium. Systematic analysis of the site of frameshifting indicates that excess tRNA_3~(Pro) promotes near-cognate decoding at CCC codons. Re-phasing of the reading frame can be achieved by a subsequent slippage of the tRNA onto a cognate codon in the +1 reading frame. Frameshifting appears to be due to an imbalance of CCC-cognate and near-cognate tRNAs, as the effect of excess tRNA_3~(Pro) on reading frame maintenance can be reversed by increasing simultaneously the concentration of the cognate tRNA_2~(Pro). Finally, the cmo~5U modification present at position 34 of tRNA_3~(Pro), which allows this tRNA to decode CCU in addition to CCG and CCA also affects frameshifting, indicating that the ability of the near-cognate tRNA to decode a cognate codon efficiently in the alternative reading frame is important for re-phasing of the reading frame.