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 journalArticle

57 Citations (Scopus)

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

Fingerprint

Complementary RNA
LDL Receptors
Chemical activation
RNA
Cholesterol
Lovastatin
Transcription Initiation Site
Cell Surface Receptors
Hypercholesterolemia
Gene expression
Liver
Display devices
Gene Expression

ASJC Scopus subject areas

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

Cite this

Activation of LDL receptor expression by small RNAs complementary to a noncoding transcript that overlaps the LDLR promoter. / Matsui, Masayuki; Sakurai, Fuminori; Elbashir, Sayda; Foster, Donald J.; Manoharan, Muthiah; Corey, David R.

In: Chemistry and Biology, Vol. 17, No. 12, 22.12.2010, p. 1344-1355.

Research output: Contribution to journalArticle

Matsui, Masayuki ; Sakurai, Fuminori ; Elbashir, Sayda ; Foster, Donald J. ; Manoharan, Muthiah ; Corey, David R. / Activation of LDL receptor expression by small RNAs complementary to a noncoding transcript that overlaps the LDLR promoter. In: Chemistry and Biology. 2010 ; Vol. 17, No. 12. pp. 1344-1355.
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