PULLING THE RIBOSOME OUT OF FRAME BY -TRANSFER-RNA(1 AT A PROGRAMMED FRAMESHIFT SITE BY COGNATE BINDING OF AMINOACYL)

Programmed translational frameshifts efficiently alter a translational reading frame by shifting the reading frame during translation. A +1 frameshift has two simultaneous requirements: a translational pause wh ich occurs when either an inefficiently recognized sense or terminatio n codon occupies the A site, and the presence of a special peptidyl-tR NA occupying the P site during the pause. The special nature of the pe ptidyl-tRNA reflects its ability either to slip +1 on the mRNA or to f acilitate binding of an incoming aminoacyl-tRNA out of frame in the A site. This second mechanism suggested that in some cases the first +1. frame tRNA could have an active role in frameshifting. We found that overproducing this tRNA can drive frameshifting, surprisingly regardle ss of whether frameshifting occurs by peptidyl-tRNA slippage or out-of -frame binding of aminoacyl-tRNA. This finding suggests that in both c ases, the shift in reading frame occurs coincident with formation of a cognate codon-anticodon interaction in the shifted frame.