生物谷报道：美国冷泉港实验室（CSHL）的科学家近日在《自然》杂志发表论文，研究发现一种新的小RNA。
科学家从果蝇体内鉴别出了一类全新的小RNA分子，并且澄清了一类此前已知的小RNA如何调控基因活性。领导该项研究的Gregory J. Hannon教授是小RNA研究的先驱，他说，“小RNA分子的类型比我们最初猜想的更多。同时，人们已知的每一类小RNA起作用的方式比此前认为的要更多。”
此前，科学家所知的果蝇体内调控小RNA只有两大类，它们与不同的蛋白发生作用。其中一类是microRNA，它们存在于整个生物体中，与Argonaute 1蛋白结合，调控许多基因的活性。另一类名为piRNA，它们只存在于性器官细胞中，与Piwi蛋白结合发挥作用。这类小RNA可以抑制遗传“入侵者”——转位（座）因子（transposable elements），保护基因组不受破坏，从而避免一些相关的疾病。
在最新研究中，Hannon和同事找到了与第三种蛋白Argonaute 2结合的RNA分子。研究人员利用了一种高效设备，它可以同时测定数百万个小RNA分子的碱基序列。这样，他们就可以扫描已知的基因组来寻找匹配的序列。研究人员发现，这些小RNA分子不同于以往所知的任何一类，它们既改变基因活性，又抑制转位因子。研究人员表示，这一发现拓展了人类已知的小RNA的“本事”，并且进一步模糊了此前两类小RNA的差异。
在另一项相关研究中，Hannon等人利用小鼠模型发现了调控RNA的新来源。许多RNA序列比如miRNA被标记为调控分子是由于它们自身的折叠。特定蛋白识别能够识别折叠产生的双链RNA，并将它们切成调控RNA片段。Hannon等人发现，这种双链RNA可以源自“伪基因”（遗留在基因组中的常基因拷贝，因功能损坏而无法表达，曾被认为是“垃圾DNA”）。研究表明，常基因的RNA拷贝有时会与相关的“伪基因”拷贝片段发生联系，产生双链RNA，它们可以激活细胞的调控机器。
新发现为人们理解小RNA影响基因活性的过程，再添加了一个复杂性层面。Hannon等人写道，“总体来看，我们的研究表明，双链RNA在进化过程中被广泛作为调控分子。”（生物谷www.bioon.com）
生物谷推荐原始出处：
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: hannon@cshl.edu) or J.B. (Email: brenneck@cshl.edu).
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.
