Where To Stop: Occurrence and Evolution of Translational Recoding Signals in RNA Viruses of Eukaryotes

Abstract

Many (+)RNA viruses employ translational recoding mechanisms, such as programmed ribosomal readthrough and ribosomal frameshifting, to direct a fraction of translating ribosomes in the infected cell to recode or bypass a stop codon in the zero reading frame and continue translation, thus producing protein isoforms with distinct functions. This creates a means to regulate both the quantity and time of synthesis of canonical and fusion proteins. The viral programmed ribosomal readthrough and ribosomal frameshifting signals are variable, with some being just short RNA sequences encompassing a stop codon, whereas others require elaborate RNA-RNA and RNA-protein interactions. Within virus evolutionary lineages, a given type of recoding signal is not universal, and its presence may be specific to a virus family, species, or even strain. It is possible that the establishment of virus recoding mechanisms and expression patterns occurs after the appearance of extant virus lineages, and these recoding signals might be acquired on multiple occasions during evolution. Recoding signals are the key regulators of gene expression in several clinically important viruses, such as human immunodeficiency viruses 1 and 2, human T-cell lymphotropic retroviruses, and severe acute respiratory syndrome coronavirus 2, as well as in a number of other animal and plant viruses of concern. The knowledge of viral recoding mechanisms is expected to provide new perspectives for the development of antiviral and synthetic biology strategies.