生物谷Bioon.com報道：美國和加拿大科學(xué)家近日研究發(fā)現(xiàn),，RNA可以與DNA上稱為啟動子區(qū)（promoter region，位于實際基因前的一小段DNA片段）的非基因區(qū)相互作用,。在基因被開啟前,，啟動子必須先被激活,。相關(guān)論文7月6日在線發(fā)表于《自然—結(jié)構(gòu)與分子生物學(xué)》（Nature Structural and Molecular Biology）上,。
在之前的研究中,，美國德州大學(xué)西南醫(yī)學(xué)中心的David Corey和Bethany Janowski發(fā)現(xiàn)，小鏈RNA能夠激活癌細(xì)胞中的某些基因,。研究人員用人造RNA證實,，它們可以通過擾亂環(huán)繞DNA的調(diào)節(jié)蛋白混合體來調(diào)控基因的表達(dá)。不過其中的具體機(jī)制一直沒有弄清,。
在最新的研究中,，研究人員發(fā)現(xiàn)了RNA一個意想不到的標(biāo)靶。RNA瞄準(zhǔn)的并不是基因本身,，而是由細(xì)胞產(chǎn)生的另一種RNA，所謂的非編碼RNA轉(zhuǎn)錄本,。它與啟動子區(qū)有關(guān)聯(lián),，啟動子區(qū)被激活的時候，就作為啟動命令開啟基因,。具體來說,，人造RNA與RNA轉(zhuǎn)錄本相綁定，然后結(jié)合其它蛋白形成RNA-蛋白質(zhì)聯(lián)合體。聯(lián)合體接著與啟動子區(qū)相綁定,，從而可以激活或抑制基因的表達(dá),。
迄今為止，很多科學(xué)家相信蛋白本身在啟動子區(qū)就可調(diào)控基因的表達(dá),，此次研究表明這種觀點不一定正確,。David Corey說：“我們對于RNA激活基因表達(dá)機(jī)制的發(fā)現(xiàn)為潛在的藥物研發(fā)提供了新的意料之外的標(biāo)靶。”
編碼蛋白的基因一旦出現(xiàn)變異,，會導(dǎo)致蛋白的缺失或過量表達(dá),，從而造成疾病。雖然用合成RNA來調(diào)控基因以達(dá)到治療疾病的目的目前還無法實現(xiàn),，不過Corey表示,，此次實驗所用的人造RNA分子已經(jīng)被用于臨床試驗，所以基因調(diào)控藥物的研發(fā)應(yīng)該會進(jìn)展很快,。（科學(xué)網(wǎng) 梅進(jìn)/編譯）
生物谷推薦原始出處：
（《自然—結(jié)構(gòu)與分子生物學(xué)》（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: [email protected]
Correspondence to: Bethany A Janowski1,2 e-mail: [email protected]
