Structure, stability and function of RNA pseudoknots involved in stimulating ribosomal frameshifting

Programmed -1 ribosomal frameshifting has become the subject of increasing interest over the last several years, due in part to the ubiquitous nature of this translational recoding mechanism in pathogenic animal and plant vir uses. All cis-acting frameshift signals encoded in mRNAs are minimally comp osed of two functional elements: a heptanucleotide "slippery sequence" conf orming to the general form X XXY YYZ,followed by an RNA structural element, usually an H-type RNA pseudoknot, positioned an optimal number of nucleoti des (5 to 9) downstream. The slippery sequence itself promotes a low level (approximate to 1%) of frameshifting; however, downstream pseudoknots stimu late this process significantly, in some cases up to 30 to 50 %. Although t he precise molecular mechanism of stimulation of frameshifting remains poor ly understood, significant advances have been made in our knowledge of the three-dimensional structures, thermodynamics of folding, and functional det erminants of stimulatory RNA pseudoknots derived from the study of several well-characterized frameshift signals. These studies are summarized here an d provide new insights into the structural requirements and mechanism of pr ogrammed -1 ribosomal frameshifting. (C) 2000 Academic Press.