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RNA 干涉 (RNAi)是從真菌到人類都保留下來(lái)的一個(gè)基因沉默機(jī)制。高吞吐量的測(cè)序方法表明，動(dòng)物和植物有大量的小非編碼RNA，其中很多的功能仍未確定。盡管RNAi通道具有保守性，但相似類型的小RNA是否在低等真核細(xì)胞中也存在卻基本上沒(méi)有人探索過(guò)。 現(xiàn)在，人們?cè)诮z狀菌“脈孢菌”中發(fā)現(xiàn)了新的一類小RNA。因其與Argonaute蛋白QDE-2的聯(lián)系，它們被命名為qiRNAs。同QDE-2一樣，它們的出現(xiàn)也是為了響應(yīng)DNA損傷。它們的長(zhǎng)度約為20個(gè)核苷酸，比“脈孢菌”的siRNA稍短一些。“脈孢菌”的siRNA突變體對(duì)DNA損傷的敏感度增加，表明qiRNAs作為蛋白翻譯的抑制因子在DNA修復(fù)中扮演一個(gè)角色。 本期封面所示為排列成玫瑰花飾形的一組“脈孢菌”子囊，它們具有發(fā)熒光的雙核囊孢子（由GFP-histone H1來(lái)指示）。 推薦原始出處： Nature 459, 274-277 (14 May 2009) | doi:10.1038/nature08041 qiRNA is a new type of small interfering RNA induced by DNA damage Heng-Chi Lee1, Shwu-Shin Chang1, Swati Choudhary1, Antti P. Aalto2, Mekhala Maiti1,3, Dennis H. Bamford2 & Yi Liu1 1 Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA 2 Institute of Biotechnology and Department of Biological and Environmental Sciences, Biocenter 2, PO Box 56, FIN-00014 University of Helsinki, Helsinki, Finland 3 Present address: Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA. RNA interference pathways use small RNAs to mediate gene silencing in eukaryotes. In addition to small interfering RNAs (siRNAs) and microRNAs, several types of endogenously produced small RNAs have important roles in gene regulation, germ cell maintenance and transposon silencing1, 2, 3, 4. The production of some of these RNAs requires the synthesis of aberrant RNAs (aRNAs) or pre-siRNAs, which are specifically recognized by RNA-dependent RNA polymerases to make double-stranded RNA. The mechanism for aRNA synthesis and recognition is largely unknown. Here we show that DNA damage induces the expression of the Argonaute protein QDE-2 and a new class of small RNAs in the filamentous fungus Neurospora crassa. This class of small RNAs, known as qiRNAs because of their interaction with QDE-2, are about 20–21 nucleotides long (several nucleotides shorter than Neurospora siRNAs), with a strong preference for uridine at the 5' end, and originate mostly from the ribosomal DNA locus. The production of qiRNAs requires the RNA-dependent RNA polymerase QDE-1, the Werner and Bloom RecQ DNA helicase homologue QDE-3 and dicers. qiRNA biogenesis also requires DNA-damage-induced aRNAs as precursors, a process that is dependent on both QDE-1 and QDE-3. Notably, our results suggest that QDE-1 is the DNA-dependent RNA polymerase that produces aRNAs. Furthermore, the Neurospora RNA interference mutants show increased sensitivity to DNA damage, suggesting a role for qiRNAs in the DNA-damage response by inhibiting protein translation. (責(zé)任編輯：Doctor001) |
