Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 USA.
Clin Epigenetics. 2011 Aug;2(2):433-7. doi: 10.1007/s13148-011-0034-6. Epub 2011 Apr 28.
Emerging evidence points to a role for long non-coding RNAs in the modulation of epigenetic states and transcription in human cells. New insights, using various forms of small non-coding RNAs, suggest that a mechanism of action is operative in human cells, which utilizes non-coding RNAs to direct epigenetic marks to homology containing loci resulting ultimately in the epigenetic-based modulation of gene transcription. Importantly, insights into this mechanism of action have allowed for certain target sequences, which are either actively involved in RNA mediated epigenetic regulation or targets for non-coding RNA based epigenetic regulation, to be selected. As such, it is now feasible to utilize small antisense RNAs to either epigenetically silence a gene expression or remove epigenetic silencing of endogenous non-coding RNAs and essentially turn on a gene expression. Knowledge of this emerging RNA-based epigenetic regulatory network and our ability to cognitively control gene expression has deep implications in the development of an entirely new area of pharmacopeia.
新兴证据表明,长非编码 RNA 在人类细胞中表观遗传状态和转录的调控中发挥作用。使用各种形式的小非编码 RNA 的新见解表明,一种作用机制在人类细胞中起作用,该机制利用非编码 RNA 将表观遗传标记导向同源包含基因座,最终导致基于表观遗传的基因转录调控。重要的是,对这种作用机制的深入了解使得某些靶序列能够被选择,这些序列要么积极参与 RNA 介导的表观遗传调控,要么是非编码 RNA 基于表观遗传调控的靶标。因此,现在可以利用小的反义 RNA 来使基因表达沉默或去除内源性非编码 RNA 的表观遗传沉默,并从实质上激活基因表达。对这一新兴的基于 RNA 的表观遗传调控网络的了解以及我们对基因表达的认知控制能力,对药理学全新领域的发展具有深远的影响。