生物谷報(bào)道：美國(guó)冷泉港實(shí)驗(yàn)室（CSHL）的科學(xué)家近日在《自然》雜志發(fā)表論文，研究發(fā)現(xiàn)一種新的小RNA,。
科學(xué)家從果蠅體內(nèi)鑒別出了一類(lèi)全新的小RNA分子,，并且澄清了一類(lèi)此前已知的小RNA如何調(diào)控基因活性。領(lǐng)導(dǎo)該項(xiàng)研究的Gregory J. Hannon教授是小RNA研究的先驅(qū),，他說(shuō),，“小RNA分子的類(lèi)型比我們最初猜想的更多。同時(shí),，人們已知的每一類(lèi)小RNA起作用的方式比此前認(rèn)為的要更多,。”
此前，科學(xué)家所知的果蠅體內(nèi)調(diào)控小RNA只有兩大類(lèi),，它們與不同的蛋白發(fā)生作用,。其中一類(lèi)是microRNA，它們存在于整個(gè)生物體中,，與Argonaute 1蛋白結(jié)合,，調(diào)控許多基因的活性。另一類(lèi)名為piRNA,，它們只存在于性器官細(xì)胞中,，與Piwi蛋白結(jié)合發(fā)揮作用,。這類(lèi)小RNA可以抑制遺傳“入侵者”——轉(zhuǎn)位（座）因子（transposable elements）,，保護(hù)基因組不受破壞，從而避免一些相關(guān)的疾病,。
在最新研究中,，Hannon和同事找到了與第三種蛋白Argonaute 2結(jié)合的RNA分子。研究人員利用了一種高效設(shè)備，它可以同時(shí)測(cè)定數(shù)百萬(wàn)個(gè)小RNA分子的堿基序列,。這樣,，他們就可以?huà)呙枰阎幕蚪M來(lái)尋找匹配的序列。研究人員發(fā)現(xiàn),，這些小RNA分子不同于以往所知的任何一類(lèi),，它們既改變基因活性，又抑制轉(zhuǎn)位因子,。研究人員表示,，這一發(fā)現(xiàn)拓展了人類(lèi)已知的小RNA的“本事”，并且進(jìn)一步模糊了此前兩類(lèi)小RNA的差異,。
在另一項(xiàng)相關(guān)研究中,，Hannon等人利用小鼠模型發(fā)現(xiàn)了調(diào)控RNA的新來(lái)源。許多RNA序列比如miRNA被標(biāo)記為調(diào)控分子是由于它們自身的折疊,。特定蛋白識(shí)別能夠識(shí)別折疊產(chǎn)生的雙鏈RNA,，并將它們切成調(diào)控RNA片段。Hannon等人發(fā)現(xiàn),，這種雙鏈RNA可以源自“偽基因”（遺留在基因組中的?；蚩截悾蚬δ軗p壞而無(wú)法表達(dá),，曾被認(rèn)為是“垃圾DNA”）,。研究表明，?；虻腞NA拷貝有時(shí)會(huì)與相關(guān)的“偽基因”拷貝片段發(fā)生聯(lián)系,，產(chǎn)生雙鏈RNA，它們可以激活細(xì)胞的調(diào)控機(jī)器,。
新發(fā)現(xiàn)為人們理解小RNA影響基因活性的過(guò)程,，再添加了一個(gè)復(fù)雜性層面。Hannon等人寫(xiě)道,，“總體來(lái)看,，我們的研究表明，雙鏈RNA在進(jìn)化過(guò)程中被廣泛作為調(diào)控分子,。”（生物谷www.bioon.com）
生物谷推薦原始出處：
Nature,，doi:10.1038/nature07007，Benjamin Czech, Gregory J. Hannon & Julius Brennecke
An endogenous small interfering RNA pathway in Drosophila
Benjamin Czech1,6, Colin D. Malone1,6, Rui Zhou2, Alexander Stark3,4, Catherine Schlingeheyde1, Monica Dus1, Norbert Perrimon2, Manolis Kellis3, James A. Wohlschlegel5, Ravi Sachidanandam1, Gregory J. Hannon1 & Julius Brennecke1
1.Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
2. Harvard Medical School, Department of Genetics, Howard Hughes Medical Institute, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
3. Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA
4. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
5. Department of Biological Chemistry, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA
6. These authors contributed equally to this work.
Correspondence to: Gregory J. Hannon1Julius Brennecke1 Correspondence and requests for materials should be addressed to G.J.H. (Email: [email protected]) or J.B. (Email: [email protected]).
Drosophila endogenous small RNAs are categorized according to their mechanisms of biogenesis and the Argonaute protein to which they bind. MicroRNAs are a class of ubiquitously expressed RNAs of 22 nucleotides in length, which arise from structured precursors through the action of Drosha–Pasha and Dicer-1–Loquacious complexes1, 2, 3, 4, 5, 6, 7. These join Argonaute-1 to regulate gene expression8, 9. A second endogenous small RNA class, the Piwi-interacting RNAs, bind Piwi proteins and suppress transposons10, 11. Piwi-interacting RNAs are restricted to the gonad, and at least a subset of these arises by Piwi-catalysed cleavage of single-stranded RNAs12, 13. Here we show that Drosophila generates a third small RNA class, endogenous small interfering RNAs, in both gonadal and somatic tissues. Production of these RNAs requires Dicer-2, but a subset depends preferentially on Loquacious1, 4, 5 rather than the canonical Dicer-2 partner, R2D2 (ref. 14). Endogenous small interfering RNAs arise both from convergent transcription units and from structured genomic loci in a tissue-specific fashion. They predominantly join Argonaute-2 and have the capacity, as a class, to target both protein-coding genes and mobile elements. These observations expand the repertoire of small RNAs in Drosophila, adding a class that blurs distinctions based on known biogenesis mechanisms and functional roles.
