A remaining question centers on whether the role of the RNA pseudoknot in À1 PRF is passive or active. In the '9 Å solution' (6), the frameshift mechanism is activated by movement of the A-site codon-anticodon complex by 1 base in the 5 0 direction upon accommodation. As currently described, the mRNA pseudoknot merely passively blocks entry of the downstream message into the ribosome, resulting in stretching of the segment of mRNA located between the codon-anticodon complex and the pseudoknot. By this model, all of the energetic input for the frameshift is derived from hydrolysis of GTP by eEF1A. However, it is possible that the pseudoknot may also actively contribute to the frameshift mechanism. Specifically, pulling the downstream message into the ribosome at accommodation could result in unwinding of Stem 1 of the pseudoknot by one additional base pair. The energetic cost of so doing would be to introduce an equivalent amount of torsional resistance into Stem 2. If Stem 2 were to release this resistance by 'pulling back', the base pair in Stem 1 would be re-formed, which in turn would contribute to the energy required to dissociate the A-and P-site codonanticodon complexes from the zero-frame. This would be followed by slippage of the mRNA by 1 base in the 3 0 direction relative to the ribosome, followed by the formation of À1 frame codon-anticodon complexes. As such, the proposed active role for the mRNA pseudoknot would further reduce the energetic barrier to À1 PRF. In sum, we suggest that the 'torsional restraint model' can be combined with the '9 Å solution' to mechanistically explain the original 'simultaneous 