The observed effects on -1 PRF are consistent with a recent kinetic analysis demonstrating that aa-tRNA slippage is the most highly weighted parameter in determining the rate at which this process occurs (Liao,P.Y. et al., submitted for publication). Here, increased affinity for aa-tRNA by the large subunit suggests that the 51-4A ribosomes stabilize the frameshifted (i.e. near-cognate) tRNAs, reducing their ability to be proofread, thus promoting increased rates of À1 PRF. This is consistent with the observed increased rates of missense decoding in this mutant. Conversely, post-slippage A-site tRNAs are even less stable in the 54-7A mutants, leading these to be more efficiently proofread, and thus promoting decreased À1 PRF efficiency. In both cases, altering À1 PRF from the optimum 'golden mean' precludes these cells from maintaining the yeast killer virus (19, 48) . Programmed +1 frameshifting is completely dependent on peptidyl-tRNA slippage. Increased +1 PRF in the 54-57A mutant is consistent with decreased affinity for this substrate. The failure to observe decreased +1 PRF in the 51-54A mutant, despite its increased affinity for peptidyl-tRNA, is not entirely clear, although this may be due to the inability of these ribosomes to achieve a threshold beyond which +1 PRF effects can be observed.