Structural highlights
Publication Abstract from PubMedExpression of the HIV reverse transcriptase and other essential viral enzymes requires a -1 translational frameshift. The frameshift event is induced by two highly conserved RNA elements within the HIV-1 mRNA: a UUUUUUA heptamer known as the slippery sequence, and a downstream RNA structure. Here, we report structural and thermodynamic evidence that the HIV-1 frameshift site RNA forms a stem-loop and lower helix separated by a three-purine bulge. We have determined the structure of the 45 nucleotide frameshift site RNA using multidimensional heteronuclear nuclear magnetic resonance (NMR) methods. The upper helix is highly thermostable (T(m)>90 degrees C), forming 11 Watson-Crick base-pairs capped by a stable ACAA tetraloop. The eight base-pair lower helix was found to be only moderately stable (T(m)=47 degrees C). A three-purine bulge separates the highly stable upper helix from the lower helix. Base stacking in the bulge forms a wedge, introducing a 60 degrees bend between the helices. Interestingly, this bend is similar to those seen in a number of frameshift inducing pseudoknots for which structures have been solved. The lower helix must denature to allow the ribosome access to the slippery site, but likely functions as a positioning element that enhances frameshift efficiency. Solution structure and thermodynamic investigation of the HIV-1 frameshift inducing element.,Staple DW, Butcher SE J Mol Biol. 2005 Jun 24;349(5):1011-23. Epub 2005 Apr 1. PMID:15927637[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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