Pseudoknot-Dependent Programmed —1 Ribosomal Frameshifting: Structures, Mechanisms and Models

Brierley, Ian; Gilbert, Robert J.C.; Pennell, Simon

Programmed —1 ribosomal frameshifting is a translational recoding strategy that takes place during the elongation phase of protein biosynthesis. Frameshifting occurs in response to specific signals in the mRNA; a slippery sequence, where the ribosome changes frame, and a stimulatory RNA secondary structure, usually a pseudoknot, located immediately downstream. During the frameshift the ribosome slips backwards by a single nucleotide (in the 5′-wards/—1 direction) and continues translation in the new, overlapping reading frame, generating a fusion protein composed of the products of both the original and the —1 frame coding regions. In eukaryotes, frameshifting is largely a phenomenon of virus gene expression and associated predominantly with the expression of viral replicases. Research on frameshifting impacts upon diverse topics, including the ribosomal elongation cycle, RNA structure and function, tRNA modification, virus replication, antiviral intervention, evolution and bioinformatics. This chapter focuses on the structure and function of frameshift-stimulatory RNA pseudoknots and mechanistic aspects of ribosomal frameshifting. A variety of models of the frameshifting process are discussed in the light of recent advances in our understanding of ribosome structure and the elongation cycle.