National Center for Biodefense and Infectious Disease, School of Systems Biology, George Mason University, 10900 University Blvd, Manassas, VA 20108, USA.
Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, 9000 Rockville Pike, Bethesda, MD 20810, USA.
Biology (Basel). 2012 Aug 24;1(2):339-69. doi: 10.3390/biology1020339.
Gene silencing via non-coding RNA, such as siRNA and miRNA, can occur at the transcriptional, post-transcriptional, and translational stages of expression. Transcriptional gene silencing (TGS) involving the RNAi machinery generally occurs through DNA methylation, as well as histone post-translational modifications, and corresponding remodeling of chromatin around the target gene into a heterochromatic state. The mechanism by which mammalian TGS occurs includes the recruitment of RNA-induced initiation of transcriptional gene silencing (RITS) complexes, DNA methyltransferases (DNMTs), and other chromatin remodelers. Additionally, virally infected cells encoding miRNAs have also been shown to manipulate the host cell RNAi machinery to induce TGS at the viral genome, thereby establishing latency. Furthermore, the introduction of exogenous siRNA and shRNA into infected cells that target integrated viral promoters can greatly suppress viral transcription via TGS. Here we examine the latest findings regarding mammalian TGS, specifically focusing on HIV-1 infected cells, and discuss future avenues of exploration in this field.
通过非编码 RNA（如 siRNA 和 miRNA）进行基因沉默可以在表达的转录、转录后和翻译阶段发生。涉及 RNAi 机制的转录基因沉默 (TGS) 通常通过 DNA 甲基化以及组蛋白翻译后修饰发生，并相应地将靶基因周围的染色质重塑为异染色质状态。哺乳动物 TGS 发生的机制包括 RNA 诱导的转录基因沉默 (RITS) 复合物、DNA 甲基转移酶 (DNMTs) 和其他染色质重塑因子的募集。此外，已经表明感染病毒的细胞编码的 miRNAs 也可以操纵宿主细胞 RNAi 机制，从而在病毒基因组上诱导 TGS，从而建立潜伏状态。此外，将针对整合病毒启动子的外源 siRNA 和 shRNA 导入感染细胞可以通过 TGS 极大地抑制病毒转录。在这里，我们检查了关于哺乳动物 TGS 的最新发现，特别是针对 HIV-1 感染细胞，并讨论了该领域未来的探索途径。
