刘一《Nature》封面 解析新型RNAi分子

　　

生物通报道，美国德克萨斯大学西南医学中心生理系，芬兰赫尔辛基大学生物科技学院生物与环境科学系以及西南医学中心细胞生物学系的研究者在最新一期的Nature上发表qiRNA is a new type of small interfering RNA induced by DNA damage文章，列为该期Nature杂志的封面文章。

 

本期封面所示为排列成玫瑰花饰形的一组“脉孢菌”子囊，它们具有发荧光的双核囊孢子（由GFP-histone H1来指示）。

 

文章通讯作者是华人科学家，德克萨斯大学西南医学中心生理系的刘一教授，刘一实验室主要从事生物昼夜节律分子机理与RNAi两方面的研究。

 

RNA 干涉 (RNAi)是从真菌到人类都保留下来的一个基因沉默机制。在RNAi过程中siRNA和其他microRNA扮演重要的角色，它们直接调控基因的表达活性。要生成这些RNA（siRNA和microRNA）必须先合成一些变体的RNA（aberrant RNAs，aRNAs）或是前体RNAs（pre-RNAs），变体RNAs和前体RNAs能被依赖于RNA的RNA聚合酶识别，指导它们合成双链RNA。然而，aRNA的合成与识别机制一直不明。

 

刘一等人发现，在丝状真菌Neurospora crassa中，当DNA受到损伤时会诱导合成Argonaute蛋白QDE-2和一类新的小RNAs(Small RNAs)，这类小RNAs能与QDE-2相互作用，由大约20-21个核苷酸组成（比脉孢菌的siRNA要少几个核苷酸），偏爱5‘端的尿核甙，大部分起源于核糖体DNA基因座上，因此被称为qiRNAs。

 

产生qiRNAs需有赖于RNA的RNA聚合酶QDE-1，the Werner and Bloom RecQ DNA helicase homologue QDE-3 以及 dicers参与。合成qiRNA的原料来自由DNA损伤所诱导产生的aRNAs，aRNAs作为qiRNA的前体，这一过程依赖于QDE-1与QDE-3。

 

研究结果表明，依赖于RNA的RNA聚合酶QDE-1是促进生成aRNA的酶。并且脉孢菌的RNAi突变常出现于DNA损伤情况下，这表明，RNAi对DNA损伤十分敏感，这也证明qiRNA是DNA损伤应答过程中的一环节，它能抑制细胞内错误蛋白的翻译，避免DNA损伤对细胞带来的伤害。

（生物通 小茜）

生物通推荐原文检索：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

 

Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA

Institute of Biotechnology and Department of Biological and Environmental Sciences, Biocenter 2, PO Box 56, FIN-00014 University of Helsinki, Helsinki, Finland

Present address: Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.

 

 

Top of pageRNA 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.