Chung Wei-Jen, Okamura Katsutomo, Martin Raquel, Lai Eric C
Department of Developmental Biology, Sloan-Kettering Institute, 521 Rockefeller Research Laboratories, 1275 York Ave, Box 252, New York, New York 10065, USA.
Curr Biol. 2008 Jun 3;18(11):795-802. doi: 10.1016/j.cub.2008.05.006. Epub 2008 May 22.
Because of the mutagenic consequences of mobile genetic elements, elaborate defenses have evolved to restrict their activity. A major system that controls the activity of transposable elements (TEs) in flies and vertebrates is mediated by Piwi-interacting RNAs (piRNAs), which are approximately 24-30 nucleotide RNAs that are bound by Piwi-class effectors. The piRNA system is thought to provide primarily a germline defense against TE activity.
Here, we describe a second system that represses Drosophila TEs by using endogenous small interfering RNAs (siRNAs), which are 21 nucleotide, 3'-end-modified RNAs that are dependent on Dicer-2 and Argonaute-2. In contrast to piRNAs, we find that the TE-siRNA system is active in somatic tissues, and particularly so in various immortalized cell lines. Analysis of the patterns and properties of TE-derived small RNAs reveals further distinctions between TE regions and genomic loci that are converted into piRNAs and siRNAs, respectively. Finally, functional tests show that many transposon transcripts accumulate to higher levels in cells and animal tissues that are deficient for Dicer-2 or Argonaute-2.
Drosophila utilizes two small-RNA systems to restrict transposon activity in the germline (mostly via piRNAs) and in the soma (mostly via siRNAs).
由于移动遗传元件具有诱变后果,因此进化出了精细的防御机制来限制其活性。在果蝇和脊椎动物中,控制转座元件(TEs)活性的一个主要系统是由Piwi相互作用RNA(piRNAs)介导的,piRNAs是大约24 - 30个核苷酸的RNA,与Piwi类效应物结合。piRNA系统被认为主要为生殖系提供针对TE活性的防御。
在这里,我们描述了第二个系统,该系统通过使用内源性小干扰RNA(siRNAs)来抑制果蝇中的TEs,siRNAs是21个核苷酸、3'末端修饰的RNA,依赖于Dicer - 2和Argonaute - 2。与piRNAs不同,我们发现TE - siRNA系统在体细胞组织中具有活性,在各种永生化细胞系中尤其如此。对TE衍生的小RNA的模式和特性分析揭示了分别转化为piRNAs和siRNAs的TE区域与基因组位点之间的进一步差异。最后,功能测试表明,在缺乏Dicer - 2或Argonaute - 2的细胞和动物组织中,许多转座子转录本积累到更高水平。
果蝇利用两种小RNA系统来限制生殖系(主要通过piRNAs)和体细胞(主要通过siRNAs)中的转座子活性。