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

Masayuki Matsui, Fuminori Sakurai, Sayda Elbashir, Donald J. Foster, Muthiah Manoharan, David R. Corey

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

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 interfere with activation of LDLR expression by lovastatin. These data demonstrate that small RNAs can activate LDLR expression and affect LDLR function.

Original languageEnglish (US)
Pages (from-to)1344-1355
Number of pages12
JournalChemistry and Biology
Volume17
Issue number12
DOIs
StatePublished - Dec 22 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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