Stem–loop structures can effectively substitute for an RNA pseudoknot in -1 ribosomal frameshifting

Yu, Chien-Hung; Noteborn, Mathieu H.; Pleij, Cornelis W. A.; Olsthoorn, René C. L.

In general, a pseudoknot is more efficient in stimulating frameshifting than a hairpin of the same sequence composition. This difference is likely related to a higher thermodynamic stability of the pseudoknot. Indeed, from thermodynamic analysis it appears that pseudoknots are more stable than their hairpin counterparts (4) (5) (6) . Recent studies employing mechanical 'pulling' of frameshifter pseudoknots have shown a correlation between the mechanical strength of a pseudoknot and its frameshifting capacity (7, 8) , and the influence of major groove and minor groove triplex structures (9) . The higher strength of a pseudoknot can be primarily attributed to the formation of base triples between the lower stem S1 and loop L2 ( Figure 1A ), making it more resistant against unwinding by an elongating ribosome (8, 10) . Base triples in several pseudoknots, such as Beet western yellows virus (BWYV) p1-p2 (11) , Pea enation mosaic virus type-1 (PEMV-1) p1-p2 (6) , Sugarcane yellow leaf virus (ScYLV) p1-p2 (12) and Simian retrovirus type-1 gagpro (SRV-1) (13, 14) have been shown to play an essential role in frameshifting. For pseudoknots with a longer stem S1 of 10-11 bp, like that of Infectious Bronchitis Virus (IBV), base triples do not appear to contribute to frameshifting (15) .