Ansari Aseem Z
Department of Biochemistry & The Genome Center of Wisconsin, University of Wisconsin-Madison, 53706, USA.
Crit Rev Biochem Mol Biol. 2009 Jan-Feb;44(1):50-61. doi: 10.1080/10409230902734044.
The paradigm of gene regulation was forever changed by the discovery that short RNA duplexes could directly regulate gene expression. Most regulatory roles attributed to noncoding RNA were often repressive. Recent observations are beginning to reveal that duplex RNA molecules can stimulate gene transcription. These RNA activators employ a wide array of mechanisms to up-regulate transcription of target genes, including functioning as DNA-tethered activation domains, as coactivators and modulators of general transcriptional machinery, and as regulators of other noncoding transcripts. The discoveries over the past few years defy "Moore's law" in the breath-taking rapidity with which new roles for noncoding RNA in gene expression are being revealed. As gene regulatory networks are reconstructed to accommodate the influence of noncoding RNAs, their importance in maintenance of cellular health will become increasingly apparent. In fact, a new generation of therapeutic agents will focus on modulating the function of noncoding RNA.
短RNA双链体能够直接调控基因表达这一发现，彻底改变了基因调控的模式。大多数归因于非编码RNA的调控作用往往具有抑制性。最近的观察结果开始揭示，双链RNA分子可以刺激基因转录。这些RNA激活剂采用多种机制上调靶基因的转录，包括作为与DNA相连的激活结构域、作为通用转录机制的共激活剂和调节剂，以及作为其他非编码转录本的调节剂。在过去几年里，非编码RNA在基因表达中的新作用被揭示的惊人速度，挑战了“摩尔定律”。随着基因调控网络被重建以适应非编码RNA的影响，它们在维持细胞健康方面的重要性将变得越来越明显。事实上，新一代治疗药物将专注于调节非编码RNA的功能。
