Morris Kevin V
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Epigenetics. 2009 Jul 1;4(5):296-301. doi: 10.4161/epi.4.5.9282. Epub 2009 Jul 17.
Epigenetic silencing of tumor suppressor gene promoters is one of the most common observations found in cancer. Despite the plethora of observed epigenetically silenced cancer related genes little is known about what is guiding the silencing to these particular loci. Two recent articles suggest that long antisense non-coding RNAs function as epigenetic regulators of transcription in human cells. These reports, along with previous observations that small antisense non-coding RNAs can epigenetically regulate transcription, imply that long antisense non-coding RNAs function as endogenous transcriptional regulatory RNAs in humans. Mechanistically, these long antisense non-coding RNAs may be involved in maintaining balanced transcription at bidirectionally transcribed loci as a method to modulate gene expression according to the selective pressures placed on the cell. The loss of this intricate bidirectional RNA based regulatory network can result in overt epigenetic silencing of gene expression. In the case of tumor suppressor genes this silencing can lead to the loss of cellular regulation and be a contributing factor in cancer. This perspective will highlight the endogenous effector RNAs and mechanism of action whereby long antisense non-coding RNAs transcriptionally regulate gene expression in human cells.
肿瘤抑制基因启动子的表观遗传沉默是癌症中最常见的现象之一。尽管观察到大量与癌症相关的基因发生了表观遗传沉默，但对于导致这些特定基因座沉默的机制却知之甚少。最近的两篇文章表明，长链反义非编码RNA在人类细胞中作为转录的表观遗传调节因子发挥作用。这些报道，以及之前关于小反义非编码RNA可通过表观遗传调控转录的观察结果，都表明长链反义非编码RNA在人类中作为内源性转录调节RNA发挥作用。从机制上讲，这些长链反义非编码RNA可能参与维持双向转录基因座的转录平衡，以此作为根据细胞所面临的选择压力来调节基因表达的一种方式。这种基于RNA的复杂双向调控网络的丧失会导致基因表达的明显表观遗传沉默。就肿瘤抑制基因而言，这种沉默会导致细胞调控功能丧失，并成为癌症的一个促成因素。本文将重点介绍长链反义非编码RNA在人类细胞中转录调控基因表达的内源性效应RNA及作用机制。
