近日,，美國(guó)冷泉港實(shí)驗(yàn)室(CSHL)的研究人員確定了一套層次分明的標(biāo)準(zhǔn),，可以解釋細(xì)胞機(jī)器如何對(duì)參與基因調(diào)控的小RNA分子前體進(jìn)行分選,。這項(xiàng)研究報(bào)告發(fā)表在Molecular Cell雜志上。
CSHL的Benjamin Czech提出一個(gè)疑問(wèn)：雙鏈RNA是否可通過(guò)不同途徑進(jìn)入RNAi通路RNAi即RNA干擾,，是由雙鏈RNA介導(dǎo)的,，由特定酶參與的特異性基因沉默現(xiàn)象，在轉(zhuǎn)錄水平,、轉(zhuǎn)錄后水平和翻譯水平上阻斷基因的表達(dá),。RNAi現(xiàn)象在生物體內(nèi)普遍存在。
長(zhǎng)的雙鏈RNA分子被Dicer酶剪切成小的雙鏈RNA分子,，隨后,，研究人員發(fā)現(xiàn)了一個(gè)可控制RNAi通路的規(guī)則，即雙鏈RNA分子被分選到Argonautes蛋白上,，該蛋白是RISC復(fù)合體(the RNA-Induced Silencing Complex)的核心部分,。
研究人員利用模式生物發(fā)現(xiàn)，當(dāng)RNA雙鏈中只有一條鏈被選擇時(shí),，將可決定小片段RNA的下一步走向,，如調(diào)控基因、或是保護(hù)細(xì)胞免于病毒的入侵,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
