Near-cognate peptidyl-tRNAs promote+1 programmed translational frameshifting in yeast

Translational frameshifting is a ubiquitous, if rare, form of alternative d ecoding in which ribosomes spontaneously shift reading frames during transl ation elongation. In studying +1 frameshifting in Ty retrotransposons of th e yeast S. cerevisiae, we previously showed that unusual P site tRNAs induc e frameshifting. The frameshift-inducing tRNAs we show here are near-cognat es for the P site codon. Their abnormal decoding induces frameshifting in e ither of two ways: weak codon-anticodon pairing allows the tRNA to disengag e from the mRNA and slip +1, or an unusual codon-anticodon structure interf eres with cognate in-frame decoding allowing out-of-frame decoding in the A site. We draw parallels between this mechanism and a proposed mechanism of frameshift suppression by mutant tRNAs.