Efficient stimulation of site-specific ribosome frameshifting by antisense oligonucleotides

RNA
Michael T HowardJohn F Atkins

Abstract

Evidence is presented that morpholino, 2'-O-methyl, phosphorothioate, and RNA antisense oligonucleotides can direct site-specific -1 translational frameshifting when annealed to mRNA downstream from sequences where the P- and A-site tRNAs are both capable of repairing with -1 frame codons. The efficiency of ribosomes shifting into the new frame can be as high as 40%, determined by the sequence of the frameshift site, as well as the location, sequence composition, and modification of the antisense oligonucleotide. These results demonstrate that a perfect duplex formed by complementary oligonucleotides is sufficient to induce high level -1 frameshifting. The implications for the mechanism of action of natural programmed translational frameshift stimulators are discussed.

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Citations

Sep 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Dustin B RitchieMichael T Woodside
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