Activation of LDL receptor expression by small RNAs complementary to a noncoding transcript that overlaps the LDLR promoter.

ABSTRACT: Low-density lipoprotein receptor (LDLR) is a cell-surface receptor that plays a central role in regulating cholesterol levels. Increased levels of LDLR would lead to reduced cholesterol levels and contribute to strategies designed to treat hypercholesterolemia. We have previously shown that duplex RNAs complementary to transcription start sites can associate with noncoding transcripts and activate gene expression. Here we show that duplex RNAs complementary to the promoter of LDLR activate expression of LDLR and increase the display of LDLR on the surface of liver cells. Activation requires complementarity to the LDLR promoter and can be achieved by chemically modified duplex RNAs. Promoter-targeted duplex RNAs can overcome repression of LDLR expression by 25-hydroxycholesterol and do not

SUBMITTER: Matsui M 

PROVIDER: S-EPMC3071588 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature