近日，美国冷泉港实验室(CSHL)的研究人员确定了一套层次分明的标准，可以解释细胞机器如何对参与基因调控的小RNA分子前体进行分选。这项研究报告发表在Molecular Cell杂志上。
CSHL的Benjamin Czech提出一个疑问：双链RNA是否可通过不同途径进入RNAi通路RNAi即RNA干扰，是由双链RNA介导的，由特定酶参与的特异性基因沉默现象，在转录水平、转录后水平和翻译水平上阻断基因的表达。RNAi现象在生物体内普遍存在。
长的双链RNA分子被Dicer酶剪切成小的双链RNA分子，随后，研究人员发现了一个可控制RNAi通路的规则，即双链RNA分子被分选到Argonautes蛋白上，该蛋白是RISC复合体(the RNA-Induced Silencing Complex)的核心部分。
研究人员利用模式生物发现，当RNA双链中只有一条链被选择时，将可决定小片段RNA的下一步走向，如调控基因、或是保护细胞免于病毒的入侵。（生物谷Bioon.com）
生物谷推荐原始出处：
Molecular Cell, 13 November 2009 doi:10.1016/j.molcel.2009.09.028
Hierarchical Rules for Argonaute Loading in Drosophila
Benjamin Czech1, 3, Rui Zhou2, 3, Yaniv Erlich1, Julius Brennecke1, 4, Richard Binari2, Christians Villalta2, Assaf Gordon1, Norbert Perrimon2, , and Gregory J. Hannon1, ,
1 Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
2 Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
Drosophila Argonaute-1 and Argonaute-2 differ in function and small RNA content. AGO2 binds to siRNAs, whereas AGO1 is almost exclusively occupied by microRNAs. MicroRNA duplexes are intrinsically asymmetric, with one strand, the miR strand, preferentially entering AGO1 to recognize and regulate the expression of target mRNAs. The other strand, miR*, has been viewed as a byproduct of microRNA biogenesis. Here, we show that miR*s are often loaded as functional species into AGO2. This indicates that each microRNA precursor can potentially produce two mature small RNA strands that are differentially sorted within the RNAi pathway. miR* biogenesis depends upon the canonical microRNA pathway, but loading into AGO2 is mediated by factors traditionally dedicated to siRNAs. By inferring and validating hierarchical rules that predict differential AGO loading, we find that intrinsic determinants, including structural and thermodynamic properties of the processed duplex, regulate the fate of each RNA strand within the RNAi pathway.
