tRNA imbalance promotes -1 frameshifting via near-cognate decoding.

tRNAGly1 is the Escherichia coli glycine tRNA specific for GGG codons. A genetic selection for multicopy suppressors of a frameshift mutation has shown that increased levels of wild-type tRNAGly1 causes -1 frameshifting. Analysis of the suppression spectrum of this multicopy suppressor and peptide sequencing of the suppressed protein product showed that it promoted GG doublet decoding at the near-cognate GGA codons. It is proposed that increasing the concentration of the GGG-specific tRNAGly1 relative to the cognate GGA-decoding tRNAGly2 allows the near-cognate tRNA to read GGA codons. Near-cognate decoding of GGA codons by tRNAGly1 can occur by a two-out-of-three reading mechanism, in which only the first two bases of the GGA codon are paired with the anticodon, thus permitting doublet translocations. In mycoplasmas, a single tRNA typically decodes all four triplets of a codon family and introduction of a feature of the Mypoplasma mycoides tRNAGly responsible for non-discriminate decoding, a C at position 32, into the anticodon E. coli tRNAGly1, enhanced the efficiency of doublet decoding. Copyright 1998 Academic Press Limited.