Efficient stimulation of site-specific ribosome frameshifting by antisense oligonucleotides.
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.
Howard
Michael T
MT
Department of Human Genetics, University of Utah, 15 N. 2030 E., Rm. 7410, Salt Lake City, UT 84112-5330, USA. mhoward@genetics.utah.edu
Gesteland
Raymond F
RF
Atkins
John F
JF
D000818:Animals; D001483:Base Sequence; D018965:Frameshifting, Ribosomal / Q000187:drug effects; D066298:In Vitro Techniques; D008156:Luciferases / Q000235:genetics; D020320:Oligoribonucleotides, Antisense / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism
D020320:Oligoribonucleotides, Antisense; D011994:Recombinant Proteins; D008156:Luciferases