Ribosome “Skipping”: “Stop-Carry On” or “StopGo” Translation

Abstract

2A and 2A-like "CHYSEL" sequences ("2As") are oligopeptides that specify ribosome "skipping" (also referred to as "Stop-Carry On" or "StopGo" translation). In this form of recoding event, the synthesis of a specific peptide bond (between the C-terminal glycine of 2A and the N-terminal proline of the downstream peptide) is skipped. We have proposed a model in which the nascent 2A oligopeptide interacts with the exit tunnel of the ribosome to stall, or pause, processivity. We propose this interaction also inhibits the mechanism of peptide bond fort-nation and that the nascent protein is released (in a stop codon-independent manner) by release factors I and 3. Translation may then "pseudo-reinitiate" at the proline codon such that two discrete translation products are formed. Although first identified within positive-stranded mammalian RNA viruses (picornaviruses), 2As are also found in a wide range of insect positive-stranded RNA viruses plus mammalian, insect and crustacean double-stranded RNA viruses. Cellular protein biogenesis may also be controlled by 2As: such sequences are also found within non-LTR retrotransposons in the genomes of trypanosomes and the purple sea urchin. 2A appears to form the N-terminal region of open reading frames of sea urchin genes encoding CATERPILLER proteins (involved in the innate immune response). Indeed, similar to 50% of such genes commence with 2A. It appears, therefore, that this form of recoding plays a role in controlling protein biogenesis both in pathogens and in the innate immune system.