摘要
MicroRNAs(miRNAs)typically bind to unstructured miRNA-binding sites in targetRNAs,leading to a mutual repression of expression.Here,we report that miR-1254interacts with structured elements in cell cycle and apoptosis regulator 1(CCAR1)5′untranslated region(UTR)and this interaction enhances the stability of both molecules.miR-1254 can also act as a repressor when binding to unstructured sites in its targets.Interestingly,structured miR-1254-targeting sites act as both a functional RNA motifsensing unit,and an independentRNA functional unit that enhances miR-1254expression.Artificially designed miRNA enhancers,termed"miRancers",can stabilize and enhance the activity of miRNAs of interest.We further demonstrate that CCAR1 5′UTR as a natural miRancer of endogenous miR-1254 re-sensitizes tamoxifen-resistant breast cancer cells to tamoxifen.Thus,our study presents a novel model of miRNA function,wherein highly structured miRancer-like motif-containing RNA fragments or miRancer molecules specifically interact with miRNAs,leading to reciprocal stabilization.
MicroRNAs(miRNAs) typically bind to unstructured mi RNA-binding sites in targetRNAs,leading to a mutual repression of expression.Here,we report that mi R-1254 interacts with structured elements in cell cycle and apoptosis regulator 1(CCAR1) 5′ untranslated region(UTR) and this interaction enhances the stability of both molecules.mi R-1254 can also act as a repressor when binding to unstructured sites in its targets.Interestingly,structured mi R-1254-targeting sites act as both a functional RNA motifsensing unit,and an independentRNA functional unit that enhances mi R-1254 expression.Artificially designed mi RNA enhancers,termed "mi Rancers",can stabilize and enhance the activity of mi RNAs of interest.We further demonstrate that CCAR1 5′ UTR as a natural mi Rancer of endogenous mi R-1254 re-sensitizes tamoxifen-resistant breast cancer cells to tamoxifen.Thus,our study presents a novel model of mi RNA function,wherein highly structured mi Rancer-like motif-containing RNA fragments or mi Rancer molecules specifically interact with mi RNAs,leading to reciprocal stabilization.
引文