Transcriptional gene silencing of dopamine D3 receptor caused by let-7d mimics in immortalized renal proximal tubule cells of rats

Gene
Ye ZhangChunyu Zeng

Abstract

Transcriptional gene silencing (TGS) induced by synthetic exogenous short interfering RNAs (siRNAs) that are fully complementary to gene promoters has been demonstrated in mammalian cells. However, it remains unclear whether microRNAs (miRNAs), which are endogenous small regulatory RNAs, can also silence gene transcription. We investigated the regulation mechanism of let-7d on dopamine D3 receptor (DRD3) in immortalized renal proximal tubule (RPT) cells of rats, where let-7d has a predicted homologous target site within DRD3 promoter. We found that let-7d mimics repressed DRD3 expression at the transcription level in RPT cells. Let-7d induced DRD3 inhibition via DNA-methyltransferase 1 (DNMT1) and DNA-methyltransferase 3b (DNMT3b) dependent DNA methylation and the inhibition could be abolished by 5'-aza-2'-deoxycytidine (5-aza-dc), a DNA methylation inhibitor. Let-7d induced DRD3 repression was associated with the recruitment of Argonaute 2 (AGO2) protein. Histone 3 lysine 9 dimethylation (H3K9me2) was involved in the let-7d induced DRD3 TGS, indicating the chromatin-level silencing. In conclusion, our results demonstrated that let-7d may induce DRD3 repression in a transcriptional manner by means of DNMTs dependent DNA methyla...Continue Reading

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Citations

Nov 9, 2016·Frontiers in Molecular Biosciences·William T CarrickJannet Kocerha
Nov 23, 2017·Frontiers in Molecular Neuroscience·Ahmad R ArshadNor Azian Abdul Murad
Oct 26, 2018·Hypertension·Gengze WuChunyu Zeng
Jan 18, 2019·Molecular Therapy. Nucleic Acids·Jia QuJian-Qiang Li
Mar 7, 2019·Journal of Chemical Information and Modeling·Chun-Chun WangJian-Qiang Li

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