Stimulation of stop codon readthrough: frequent presence of an extended 3' RNA structural element

Firth, Andrew E.; Wills, Norma M.; Gesteland, Raymond F.; Atkins, John F.

Besides the known structure-stimulated RT cases discussed above, RNA structure also plays an integral role in the recoding of UGA codons for selenocysteine insertion. In eukaryotes, this process is dependent on an RNA stem-loop structure containing specific nucleotide motifs, known as the SECIS element, usually located in the 3 0 -UTR of the corresponding mRNAs (5,6). In certain cases, an additional stem-loop structure close to the recoded stop codon has also been identified (79, 80) . For example, in the human SEPN1 gene there is a phylogenetically conserved 16 bp stem (with a 1 nt symmetric bulge) and a 5 nt loop, separated from the UGA by a 6 nt spacer. Interestingly, this structure has been shown to stimulate RT in cell culture (but not in vitro) even when the SECIS element is absent. Howard et al. located potential 3 0 -adjacent structures for at least 5 of 36 human selenocysteine-encoding UGA codons analyzed. However, their initial computational selection involved RNA-folding of just nucleotides +1 to +60 of the human sequence-an analysis which would have missed most of the 3 0 RNA structures predicted in this report. Thus 3 0 -adjacent structures may be a feature of a larger proportion of selenocysteine RT sites than these, though it does not appear to be an essential feature for selenocysteine RT (61) .