PROGRAMMED TRANSLATIONAL FRAMESHIFTING

Errors that alter the reading frame occur extremely rarely during tran slation, yet some genes have evolved sequences that efficiently induce frameshifting. These sequences, termed programmed frameshift sites, m anipulate the translational apparatus to promote non-canonical decodin g. Frameshifts are mechanistically diverse. Most cause a -1 shift of f rames; the first such site was discovered in a metazoan retrovirus, bu t they are now known to be dispersed quite widely among evolutionarily diverse species. +1 frameshift sites are much less common, but again dispersed widely. The rarest form are the translational hop sites whic h program the ribosome to bypass a region of several dozen nucleotides . Each of these types of events are stimulated by distinct mechanisms. All of the events share a common phenomenology in which the programme d frameshift site causes the ribosome to pause during elongation so th at the kinetically unfavorable alternative decoding event can occur. D uring this pause most frameshifts occur because one or more ribosome-b ound tRNAs slip between cognate or near-cognate codons. However, even this generalization is not entirely consistent, since some frameshifts occur without slippage. Because of their similarity to rarer translat ional errors, programmed frameshift sites provide a tool with which to probe the mechanism of frame maintenance.