22 Regulation of Termination and Recoding

Abstract

Precise translation of mRNA sequence into protein is a universal requirement for all living organisms. Although this would appear to require strict adherence to the linear readout of mRNAs, the term “recoding” defines a group of molecular mechanisms that alter the interpretation of hardwired sequences. Ribosomal frameshifting, termination readthrough, and incorporation of selenocysteine and pyrrolysine are examples of recoding, studies of which provide insights into the fundamental rules governing translational fidelity. Although monocistronic mRNAs are preferentially used by eukaryotes, the mRNAs of many RNA viruses encode multiple gene products. In the late 1970s, tryptic analyses of a number of retroviral proteins indicated that their Gag and Gag-Pol proteins had the same amino termini. Multiple mechanisms, including RNA splicing, termination suppression, and recoding were proposed to account for these observations. Subsequently, Gag-Pol production for a number of retroviruses and retrotransposons was shown to be due to recoding or frameshifting events (for review, see Jacks 1990). Similarly, selenocysteine was identified in glutathione peroxidase 1 in the early 1970s, but its incorporation via recoding of UGA was not revealed until 1986 (Chambers et al. 1986). Since then, translational recoding has been found to regulate gene expression in cellular mRNAs and a wide variety of RNA viruses, which may also present targets for the development of new antibiotic and antiviral therapies. A developing body of knowledge also suggests that these mechanisms may be used to posttranscriptionally regulate mRNAs of cellular origin, which has implications for expanding our understanding of developmental biology and cancer. Here...