than the first and second nucleotides. In this model, the motif structure is explained by the fact that the first and second positions of the anticodons must be able to pair perfectly in both the 0 and −1 frames. Therefore, nucleotides 2 and 1 must be identical, and nucleotides 3 and 2 must also be identical, leading to a required sequence of 3 identical nucleotides for each tRNA that slips. +1 ribosomal frameshifting The slippery sequence for a +1 frameshift signal does not have the same motif, and instead appears to function by pausing the ribosome at a sequence encoding a rare amino acid. Ribosomes do not translate proteins at a steady rate, regardless of the sequence. Certain codons take longer to translate, because there are not equal amounts of tRNA of that particular codon in the cytosol. Due to this lag, there exist in small sections of codons sequences that control the rate of ribosomal frameshifting. Specifically, the ribosome must pause to wait for the arrival of a rare tRNA, and this increases the kinetic favorability of the ribosome and its associated tRNA slipping into the new frame. In this model, the change in reading frame is caused by a single tRNA slip rather than two. Controlling mechanisms Ribosomal frameshifting may be controlled by mechanisms found in the mRNA sequence (cis-acting). This generally refers to a slippery sequence, a RNA secondary structure, or both. A −1 frameshift signal consists of both elements separated by a spacer region typically 5–9 nucleotides long. Frameshifting may also be induced by other molecules which interact with the ribosome or the mRNA (trans-acting). Frameshift signal elements Slippery sequence Slippery sequences can potentially make the reading ribosome "slip" and skip a number of nucleotides (usually only 1) and read a completely different frame thereafter. In programmed −1 ribosomal frameshifting, the slippery sequence fits a X_XXY_YYH motif, where XXX is any three identical nucleotides (though some exceptions occur), YYY typically represents UUU or AAA, and H is A, C or U. In the case of +1 frameshifting, the slippery sequence contains codons for which the corresponding tRNA is more rare, and the frameshift is favored because the codon in the new frame has a more common associated tRNA. One example of a slippery sequence is the polyA on mRNA, which is known to induce ribosome slippage even in the absence of any other elements. RNA secondary