Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes
Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes
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DOI：
10.1038/nature06904
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发表时间：
2008-05-22
期刊：
影响因子：
64.8
通讯作者：
Hannon, Gregory J.
中科院分区：
文献类型：
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作者：
Tam, Oliver H.;Aravin, Alexei A.;Hannon, Gregory J.
假基因将哺乳动物的基因组填充，作为将Messenger RNA的人为掺入转座子途径的遗迹（1）。在这里，我们表明，假基因的一部分会在小鼠卵母细胞中产生内源性的小干扰RNA（endo-siRNA）。这些内部siRNA通常是由从蛋白质编码基因到来自同源假基因的反义转录本的剪接转录本杂交形成的双链RNA处理的。倒的重复假基因也可以直接产生丰富的小RNA。第二类内孢子虫可以与PIWI相互作用的RNA一起强制对移动遗传元件进行抑制。 DICER的损失是小小的RNA不可或缺的蛋白质积分，它增加了内塞纳靶标的表达，表明其调节活性。我们的发现表明，假基因通过RNA干扰途径调节基因表达的功能，并且可能部分解释了保存哺乳动物中的Argonautemedemed催化的进化压力。
Pseudogenes populate the mammalian genome as remnants of artefactual incorporation of coding messenger RNAs into transposon pathways(1). Here we show that a subset of pseudogenes generates endogenous small interfering RNAs (endo-siRNAs) in mouse oocytes. These endo-siRNAs are often processed from double-stranded RNAs formed by hybridization of spliced transcripts from protein-coding genes to antisense transcripts from homologous pseudogenes. An inverted repeat pseudogene can also generate abundant small RNAs directly. A second class of endosiRNAs may enforce repression of mobile genetic elements, acting together with Piwi-interacting RNAs. Loss of Dicer, a protein integral to small RNA production, increases expression of endosiRNA targets, demonstrating their regulatory activity. Our findings indicate a function for pseudogenes in regulating gene expression by means of the RNA interference pathway and may, in part, explain the evolutionary pressure to conserve argonautemediated catalysis in mammals.