23 Regulatory Recoding

Abstract

Some messenger RNAs encode not only an amino acid sequence, but also special signals that alter the mechanism of ribosomal readout. These programmed alterations of decoding, termed recoding, include ribosomal frameshifts at particular sites, reading of stop codons as sense, and ribosomal jumping where some nucleotides are skipped in the mRNA. Recoding by frameshifting and stop codon read-through (Gesteland et al. 1992) is now known to be quite widely used for gene expression. In most cases, the function is to provide a set ratio between two products that have a common amino-terminal sequence. However, there are some cases where regulation is operative. Two known cases of autoregulatory frameshifting are in decoding the genes for mammalian antizyme and Escherichia coli release factor 2 (RF2). In other cases, frameshifting is part of a regulatory pathway. The level of frameshifting in yeast transposable elements and some bacterial insertion sequences is responsive to the physiological state of the cell and in turn governs the level of element mobility. Regulatory roles are only suspected in some of the other cases of frameshifting and stop codon read-through.

In programmed frameshifting, ribosomes initiate translation in the zero frame and translate conventionally to the shift site where some fraction of them are directed to one of the other two frames (+1 or −1) where they continue to the next stop codon in the new frame. Typically, only a minority of the ribosomes shift frame, whereas the majority continue on in the zero frame. The result is two protein...