Bulges and mismatches are known to change twisting and bending of a regular stem and are thus expected to influence the way in which a ribosome encounters a hairpin structure (11, 30) . To investigate a possible effect of helical twisting and bending on frameshifting, we introduced mismatches and bulges in the 12 bp stem at a position corresponding to the junction in the SRV pseudoknot ( Figure 3A) . Introduction of an A · A mismatch halfway through the stem (11 bp/AA) decreased frameshifting about 10 fold, although its predicted thermodynamic stability of À25.1 kcal/mol is comparable to that of a regular hairpin of 10 bp, yielding 13% frameshifting ( Figure 2B ). The frameshift inducing ability was recovered when the base pair was restored to A-U (12 bp/AU).