6月14日,Science杂志在线报道了线虫piRNAs研究最新进展。Piwi-相互作用RNA(piRNAs)是维持生殖细胞系完整性和可育性所必须的一类小分子RNA,但其作用机制尚不明确。
本研究证实,线虫piRNAs以不完全互补的方式,反式沉默转录物的表达。这种靶向性沉默,是不依赖于Piwi核酸内切酶活性或剪切的。相反,piRNAs引发了一种局限性二级内源小干扰RNA(endo-siRNA)反应。内源蛋白编码基因和转座子转录物在与piRNAs互补的位点发生Piwi依赖的endo-siRNA反应。而Piwi的突变则可解除这种抑制。piRNAs生物合成的基因组位点缺乏蛋白编码基因,且常与转座子的起始和末端序列分别以有义或反义方式重叠。
该研究结果提示,线虫类piRNA基因簇是为抵抗移动性DNA元件而进化出来的。由此,piRNA在线虫体内提供了可遗传的,序列特异性RNAi的驱动因子。(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.