生物谷Bioon.com报道：美国和加拿大科学家近日研究发现，RNA可以与DNA上称为启动子区（promoter region，位于实际基因前的一小段DNA片段）的非基因区相互作用。在基因被开启前，启动子必须先被激活。相关论文7月6日在线发表于《自然—结构与分子生物学》（Nature Structural and Molecular Biology）上。
在之前的研究中，美国德州大学西南医学中心的David Corey和Bethany Janowski发现，小链RNA能够激活癌细胞中的某些基因。研究人员用人造RNA证实，它们可以通过扰乱环绕DNA的调节蛋白混合体来调控基因的表达。不过其中的具体机制一直没有弄清。
在最新的研究中，研究人员发现了RNA一个意想不到的标靶。RNA瞄准的并不是基因本身，而是由细胞产生的另一种RNA，所谓的非编码RNA转录本。它与启动子区有关联，启动子区被激活的时候，就作为启动命令开启基因。具体来说，人造RNA与RNA转录本相绑定，然后结合其它蛋白形成RNA-蛋白质联合体。联合体接着与启动子区相绑定，从而可以激活或抑制基因的表达。
迄今为止，很多科学家相信蛋白本身在启动子区就可调控基因的表达，此次研究表明这种观点不一定正确。David Corey说：“我们对于RNA激活基因表达机制的发现为潜在的药物研发提供了新的意料之外的标靶。”
编码蛋白的基因一旦出现变异，会导致蛋白的缺失或过量表达，从而造成疾病。虽然用合成RNA来调控基因以达到治疗疾病的目的目前还无法实现，不过Corey表示，此次实验所用的人造RNA分子已经被用于临床试验，所以基因调控药物的研发应该会进展很快。（科学网 梅进/编译）
生物谷推荐原始出处：
（《自然—结构与分子生物学》（Nature Structural and Molecular Biology），doi:10.1038/nsmb.1444，David R Corey，Bethany A Janowski）
Article abstract
Nature Structural & Molecular Biology
Published online: 6 July 2008 | doi:10.1038/nsmb.1444
Antisense transcripts are targets for activating small RNAs
Jacob C Schwartz1,2, Scott T Younger1,2, Ngoc-Bich Nguyen1,2, Daniel B Hardy3, Brett P Monia4, David R Corey1,2 & Bethany A Janowski1,2
Abstract
Agents that activate expression of specific genes to probe cellular pathways or alleviate disease would go beyond existing approaches for controlling gene expression. Duplex RNAs complementary to promoter regions can repress or activate gene expression. The mechanism of these promoter-directed antigene RNAs (agRNAs) has been obscure. Other work has revealed noncoding transcripts that overlap mRNAs. The function of these noncoding transcripts is also not understood. Here we link these two sets of enigmatic results. We find that antisense transcripts are the target for agRNAs that activate or repress expression of progesterone receptor (PR). agRNAs recruit Argonaute proteins to PR antisense transcripts and shift localization of the heterogeneous nuclear ribonucleoprotein-k, RNA polymerase II and heterochromatin protein 1. Our data demonstrate that antisense transcripts have a central role in recognition of the PR promoter by both activating and inhibitory agRNAs.
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041, USA
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041, USA.
Department of Obstetrics and Gynaecology, and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada.
Isis Pharmaceutical, 1896 Rutherford Court, Carlsbad, California 92008, USA.
Correspondence to: David R Corey1,2 e-mail: david.corey@utsouthwestern.edu
Correspondence to: Bethany A Janowski1,2 e-mail: bethany.janowski@utsouthwestern.edu
