与重叠低密度脂蛋白受体（LDLR）启动子的非编码转录本互补的小RNA激活LDL受体表达。
Activation of LDL receptor expression by small RNAs complementary to a noncoding transcript that overlaps the LDLR promoter.
作者信息
Matsui Masayuki, Sakurai Fuminori, Elbashir Sayda, Foster Donald J, Manoharan Muthiah, Corey David R
机构信息
Departments of Pharmacology and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9041, USA.
出版信息
Chem Biol. 2010 Dec 22;17(12):1344-55. doi: 10.1016/j.chembiol.2010.10.009.
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.
低密度脂蛋白受体（LDLR）是一种细胞表面受体，在调节胆固醇水平中起核心作用。LDLR水平升高会导致胆固醇水平降低，并有助于治疗高胆固醇血症的策略。我们之前已经表明，与转录起始位点互补的双链RNA可以与非编码转录本结合并激活基因表达。在这里，我们表明与LDLR启动子互补的双链RNA激活LDLR的表达，并增加LDLR在肝细胞表面的展示。激活需要与LDLR启动子互补，并且可以通过化学修饰的双链RNA来实现。靶向启动子的双链RNA可以克服25-羟基胆固醇对LDLR表达的抑制，并且不干扰洛伐他汀对LDLR表达的激活。这些数据表明小RNA可以激活LDLR表达并影响LDLR功能。
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