Programmed Translational Frameshifting

Abstract

▪ Abstract Errors that alter the reading frame occur extremely rarely during translation, yet some genes have evolved sequences that efficiently induce frameshifting. These sequences, termed programmed frameshift sites, manipulate the translational apparatus to promote non-canonical decoding. Frameshifts are mechanistically diverse. Most cause a −1 shift of frames; the first such site was discovered in a metazoan retrovirus, but 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 which 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 programmed frameshift site causes the ribosome to pause during elongation so that the kinetically unfavorable alternative decoding event can occur. During this pause most frameshifts occur because one or more ribosome-bound 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 translational errors, programmed frameshift sites provide a tool with which to probe the mechanism of frame maintenance.

Ribosome‐mediated translational pause and protein domain organization

“…Occurrence of small hairpin stem (in which RNA loops back to form base paired interactions with a 5' region) structures in the immediate positions downstream of codons has been hypothesized to increase the time of translocation from the A to P site on the ribosome (Shpaer, 1985). The stem-loop structures on mRNA have been suggested as stimulators of ribosome pause to effect not only programmed translational frameshifts, but also other unusual "recoding" events during translation such as selenocysteine incorporation, ribosome hopping on mRNA, and readthrough of translation-termination signals (Gesteland et al, 1992;Farabaugh, 1996). In this study, we find that domain ends are preferentially coded by translationally slow mRNA regions and it would be noteworthy if such slow regions were also involved in secondary structure formation.…”

“…The 165 WC base pairs are distributed as 88 G-C and 77 A-U. Thus, the data illustrate that the slow regions can form secondary structures that might provide an additional time pause (Shpaer, 1985;Gesteland et al, 1992;Tu et al, 1992;Farabaugh, 1996) for the movement of the ribosome on the mRNA at the critical regions that encode protein domain boundaries.…”

Identification and characterization of a -1 reading frameshift in the heavy chain constant region of an IgG1 recombinant monoclonal antibody produced in CHO cells

“…18,36 On the translation level, erroneous movements of ribosomes can also lead to frameshifts. 23,24,[37][38][39][40][41] Such frameshifts can be divided into programmed frameshift (PFS) and incidental frameshift. 31,42 Programmed frameshifts typically occur at higher efficiency (up to 100%) and often produce alternative functional proteins that form an integral part of the organism's physiology.…”

“…31,42 Programmed frameshifts typically occur at higher efficiency (up to 100%) and often produce alternative functional proteins that form an integral part of the organism's physiology. 23 A programed frameshift signal is characterized by a slippery sequence on the mRNA where the frameshift actually takes place, and a stimulatory RNA structure such as stem loop, pseudoknot, or rare codons, 31,38,40 which are thought to cause the ribosome to pause allowing partition of the out-of-frame translation to occur. 43 For -1 PFS, the predominant slippery site is characterized by a heptanucleotide motif X XXX YYY Z (where X denotes any nucleotide, Y denotes A or U, and Z is A, U, or C).…”

Web Service for Finding Ribosomal Frameshifts

“…The most common type is a -1 frameshift, in which the ribosome slips a single nucleotide in the upstream direction. +1 frameshifts are much less common than -1 frameshifts, but have been observed in diverse organisms [8]. FSFinder is written in Microsoft C# and is executable on Windows systems only.…”