The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oupjournals.org stem-loop structures, it does not answer the question of how the mRNA pseudoknot directs the ribosome to pause at the correct position along the mRNA. A complementary 'torsional restraint' model addresses this issue (11) . When a stem-loop structure is unwound by an elongating ribosome, unwinding of the stem forces the loop to rotate. Since a simple stem-loop is not restrained, the loop can rotate freely and only the base pairs within the stem resist ribosomal movement, and thus the potential energy of unwinding should be distributed along the length of Stem 1 ( Figure 1A ). However, if the loop is anchored or restrained, as it is in a pseudoknot by Stem 2, since the intrinsic ribosomal helicase is processive (12) , Stem 1 cannot be fully unwound until Stem 2 is first denatured. Mechanically, as the ribosome begins to unwind the base of Stem 1, Stem 2 forces the supercoiling in the remainder of Stem 1, providing extra resistance to ribosome movement. At some specific point, the resistance to ribosome movement provided by the supercoiling counteracts the forward movement of the ribosome, increasing the likelihood that the ribosome will stop at a precise point along the mRNA. Energetically, since full unwinding of Stem 1 is dependent on complete denaturation of Stem 2, the potential energy of unwinding of the pseudoknot structure should similarly be directed toward one point. Viewed either mechanically or energetically, this point is where ribosomes will be directed to specifically pause on the mRNA. If it occurs with the tRNAs in ribosomal A-and P-sites positioned at the slippery site, then frameshifting is stimulated. This is summarized in Figure 1B . The efficiency of À1 PRF can thus be viewed as a function of (i) the fraction of ribosomes paused over the slippery site and (ii) the rate at which the structure can be denatured. There is increasing evidence from single molecule experiments that unfolding occurs in quick 'rips' at a particular force (13) , suggesting that in the case of unfolding pseudoknots, frameshifting efficiency is related to both the energy barriers to unfolding the pseudoknot structure and the resistance of the structure against the force of the ribosome. In the context of the torsional restraint model, this resistance is dependent on the ability of Stem 2 to remain intact while Stem 1 is being unwound.