Fully modified 2 ' MOE oligonucleotides redirect polyadenylation

Many genes have been described and characterized that have alternative poly adenylation signals at the 3'-end of their pre-mRNAs, Many of these same me ssages also contain destabilization motifs responsible for vapid degradatio n of the mRNA. Polyadenylation site selection can thus determine the stabil ity of an mRNA, Fully modified 2'-O-methoxy ethyl/phosphorothioate oligonuc leotides that hybridize to the 3'-most polyadenylation site or signal of E- selectin were able to inhibit polyadenylation at this site and redirect it to one of two upstream cryptic sites. The shorter transcripts produced afte r antisense treatment have fewer destabilization sequences, increased mRNA stability and altered protein expression. This study demonstrates that anti sense oligonucleotides can be successfully employed to redirect polyadenyla tion. This is the first demonstration of the use of oligonucleotides to inc rease, rather than decrease, abundance of a message.