6月14日,Science雜志在線報道了線蟲piRNAs研究最新進展,。Piwi-相互作用RNA(piRNAs)是維持生殖細胞系完整性和可育性所必須的一類小分子RNA,但其作用機制尚不明確,。
本研究證實,,線蟲piRNAs以不完全互補的方式,反式沉默轉(zhuǎn)錄物的表達,。這種靶向性沉默,,是不依賴于Piwi核酸內(nèi)切酶活性或剪切的。相反,,piRNAs引發(fā)了一種局限性二級內(nèi)源小干擾RNA(endo-siRNA)反應(yīng),。內(nèi)源蛋白編碼基因和轉(zhuǎn)座子轉(zhuǎn)錄物在與piRNAs互補的位點發(fā)生Piwi依賴的endo-siRNA反應(yīng)。而Piwi的突變則可解除這種抑制,。piRNAs生物合成的基因組位點缺乏蛋白編碼基因,,且常與轉(zhuǎn)座子的起始和末端序列分別以有義或反義方式重疊,。
該研究結(jié)果提示,線蟲類piRNA基因簇是為抵抗移動性DNA元件而進化出來的,。由此,,piRNA在線蟲體內(nèi)提供了可遺傳的,序列特異性RNAi的驅(qū)動因子,。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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Function, Targets, and Evolution of Caenorhabditis elegans piRNAs
Marloes P. Bagijn1,*, Leonard D. Goldstein1,*,?, Alexandra Sapetschnig1,*, Eva-Maria Weick1, Samir Bouasker2, Nicolas J. Lehrbach1, Martin J. Simard2, Eric A. Miska1,?
Piwi-interacting RNAs (piRNAs) are small RNAs required to maintain germline integrity and fertility, but their mechanism of action is poorly understood. Here, we demonstrate that C. elegans piRNAs silence transcripts in trans through imperfectly complementary sites. Target silencing is independent of Piwi endonuclease activity or “slicing.” Instead, piRNAs initiate a localized secondary endogenous small interfering RNA (endo-siRNA) response. Endogenous protein-coding gene and transposon transcripts exhibit Piwi-dependent endo-siRNAs at sites complementary to piRNAs and are de-repressed in Piwi mutants. Genomic loci of piRNA biogenesis are depleted of protein-coding genes and tend to overlap the start and end of transposons in sense and antisense, respectively. Our data suggest that nematode piRNA clusters are evolving to generate piRNAs against active mobile elements. Thus, piRNAs provide heritable, sequence-specific triggers for RNAi in C. elegans.