Efficient ribosomal frameshifting generally requires the presence of an RNA secondary structure to enhance the effects of the slippery sequence. The RNA structure (which can be a stem-loop or pseudoknot) is thought to pause the ribosome on the slippery site during translation, forcing it to relocate and continue replication from the −1 position. It is believed that this occurs because the structure physically blocks movement of the ribosome by becoming stuck in the ribosome mRNA tunnel. This model is supported by the fact that strength of the pseudoknot has been positively correlated with the level of frameshifting for associated mRNA.
Below are examples of predicted secondary structures for frameshift elements shown to stimulate frameshifting in a variety of organisms. The majority of the structures shown are stem-loops, with the exception of the ALIL (apical loop-internal loop) pseudoknot structure. In these images, the larger and incomplete circles of mRNA represent linear regions. The secondary "stem-loop" structures, where "stems" are formed by a region of mRNA base pairing with another region on the same strand, are shown protruding from the linear DNA. The linear region of the HIV ribosomal frameshift signal contains a highly conserved UUU UUU A slippery sequence; many of the other predicted structures contain candidates for slippery sequences as well.
The mRNA sequences in the images can be read according to a set of guidelines. While A, T, C, and G represent a particular nucleotide at a position, there are also letters that represent ambiguity which are used when more than one kind of nucleotide could occur at that position. The rules of the International Union of Pure and Applied Chemistry (IUPAC) are as follows:
These symbols are also valid for RNA, except with U (uracil) replacing T (thymine).