A Novel Regulation Method of mRNA by Recruiting Regnase-1 Using Binding Motif-Antisense Oligonucleotide Conjugates

In the present study, a novel regulation method of mRNA using RNA stem-loop motif (SL) which is recognized by Regnase-1, an endoribonuclease responsible for suppression of inflammatory mRNAs, is described.Antisense oligonucleotides (ASO) linked to SL, ASO-SLs targeting KRAS mRNA codon 12 were prepared and suppression of KRAS mRNA by ASO-SLs was evaluated.ASO-3SL containing SL linked to 2'-OMeRNA ASO targeting KRASwt at its 3'-end suppressed KRAS wt mRNA 49.2% at 100nM and 66.8% at 1M, respectively.On the other hand, ASO-5SL containing SL linked to 2'-OMeRNA ASO at its 5'-end did not affect KRAS wt expression at all at 1M.