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Efficient stimulation of site-specific ribosome frameshifting by antisense oligonucleotides

Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112-5330, USA

Reprint requests to: Michael T. Howard, Department of Human Genetics, University of Utah, 15 N. 2030 E., Rm. 7410, Salt Lake City, UT 84112-5330, USA; e-mail: mhoward{at}genetics.utah.edu; fax: (801) 585-3910.

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.

Keywords: frameshifting; antisense; morpholino; phosphorothioate; 2'-O-methyl; recoding

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