25 Programmed Translational Frameshifting, Hopping, and Readthrough of Termination Codons

Abstract

The conventional understanding of the term translational control is that it refers to an effect occurring during translation which causes a change in the amount of completed product protein per unit amount of mRNA. This chapter concerns a different type of translational control, one in which the effect of the control is to regulate the structure of the encoded protein. Genes that use programmed translational frameshifting or programmed readthrough of termination codons produce two primary translation products. The first is a protein decoded from the gene using the canonical rules of translation, corresponding one-to-one to the sequence of codons in the mRNA. The second product has a structure not predicted by the mRNA sequence, because at a discrete point in the mRNA the rules of translation are changed to allow a shift in reading frame or bypassing of a termination codon. For this type of alternative decoding, also called recoding, genes can use any of a variety of mechanisms to subvert normal translational elongation. The mechanisms employed interfere with translational fidelity so they may illuminate how ribosomes normally maintain accuracy. The purpose of recoding can be to create a second form of a protein used in a morphogenetic process, to autogenously control gene expression, or to provide alternative enzymatic activities.

The phenomena of suppression and recoding appear on their face to be unrelated. Suppression, either of nonsense or frameshift mutations, results from a permanent change to a translational component that results in occasional misapplication of the rules of translation: Ribosomes...