Intriguingly, we found that a 9 bp stem capped with a GAAA tetraloop is 2-fold less efficient in inducing frameshifting than its UUCG counterpart in vitro and in vivo. It has been reported that GAAA tetraloops are frequently involved in RNA tertiary interactions (42) . We hypothesize that the GAAA tetraloop may be involved in an unknown RNA tertiary structure with ribosomal RNA, thereby interfering with frameshifting. The fact that in the known natural examples of frameshifter hairpins, the GAAA tetraloop, despite its high stability, is absent can be taken as support for this hypothesis (Olsthoorn, unpublished data) . Further investigation of this observation may lead to new insights in ribosomal frameshifting.