Reprogramming ribosomes during viral protein synthesis

It is estimated that ~10³¹ viruses exist on planet earth, and all are entirely dependent on host cell ribosomes for viral mRNA translation. Ribosomes, the engines of protein synthesis, can be regarded as the 'compilers' of life-responsible for interpreting the genetic instruction set in a consistent way and creating protein molecules with executive functions, each of which contributes towards the phenotype of the cell. Even subtle changes in how the ribosome normally operates can have dramatic consequences, as illustrated by the lethality of many antibiotics that target the protein synthesis machinery. For viruses, millions of years of evolutionary pressure have led to every possible avenue being explored to optimise the encoding of information within a (typically) small genome. This has led to the emergence of mechanisms to reprogram translation in a variety of ways, collectively termed 'recoding'. For example, elongating ribosomes can be induced to shift reading frame and access overlapping coding sequences or to continue elongating through a stop codon. Here, we review the discovery of these phenomena, explore the role of RNA structures in these processes, and outline mechanistic questions that remain unanswered.