Ghildiyal Megha, Seitz Hervé, Horwich Michael D, Li Chengjian, Du Tingting, Lee Soohyun, Xu Jia, Kittler Ellen L W, Zapp Maria L, Weng Zhiping, Zamore Phillip D
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Science. 2008 May 23;320(5879):1077-81. doi: 10.1126/science.1157396. Epub 2008 Apr 10.
Small interfering RNAs (siRNAs) direct RNA interference (RNAi) in eukaryotes. In flies, somatic cells produce siRNAs from exogenous double-stranded RNA (dsRNA) as a defense against viral infection. We identified endogenous siRNAs (endo-siRNAs), 21 nucleotides in length, that correspond to transposons and heterochromatic sequences in the somatic cells of Drosophila melanogaster. We also detected endo-siRNAs complementary to messenger RNAs (mRNAs); these siRNAs disproportionately mapped to the complementary regions of overlapping mRNAs predicted to form double-stranded RNA in vivo. Normal accumulation of somatic endo-siRNAs requires the siRNA-generating ribonuclease Dicer-2 and the RNAi effector protein Argonaute2 (Ago2). We propose that endo-siRNAs generated by the fly RNAi pathway silence selfish genetic elements in the soma, much as Piwi-interacting RNAs do in the germ line.
小干扰RNA(siRNAs)在真核生物中指导RNA干扰(RNAi)。在果蝇中,体细胞从外源双链RNA(dsRNA)产生siRNAs,作为抵御病毒感染的防御机制。我们鉴定出了长度为21个核苷酸的内源性siRNAs(endo-siRNAs),它们对应于黑腹果蝇体细胞中的转座子和异染色质序列。我们还检测到了与信使RNA(mRNAs)互补的endo-siRNAs;这些siRNAs不成比例地映射到预测在体内形成双链RNA的重叠mRNAs的互补区域。体细胞endo-siRNAs的正常积累需要产生siRNA的核糖核酸酶Dicer-2和RNAi效应蛋白Argonaute2(Ago2)。我们提出,果蝇RNAi途径产生的endo-siRNAs使体细胞中的自私遗传元件沉默,就像Piwi相互作用RNA在生殖系中所起的作用一样。