RNA Therapeutics Institute, Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
RNA Therapeutics Institute, Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Mol Cell. 2018 Sep 6;71(5):775-790.e5. doi: 10.1016/j.molcel.2018.08.007.
In animals, PIWI-interacting RNAs (piRNAs) guide PIWI proteins to silence transposons and regulate gene expression. The mechanisms for making piRNAs have been proposed to differ among cell types, tissues, and animals. Our data instead suggest a single model that explains piRNA production in most animals. piRNAs initiate piRNA production by guiding PIWI proteins to slice precursor transcripts. Next, PIWI proteins direct the stepwise fragmentation of the sliced precursor transcripts, yielding tail-to-head strings of phased precursor piRNAs (pre-piRNAs). Our analyses detect evidence for this piRNA biogenesis strategy across an evolutionarily broad range of animals, including humans. Thus, PIWI proteins initiate and sustain piRNA biogenesis by the same mechanism in species whose last common ancestor predates the branching of most animal lineages. The unified model places PIWI-clade Argonautes at the center of piRNA biology and suggests that the ancestral animal-the Urmetazoan-used PIWI proteins both to generate piRNA guides and to execute piRNA function.
在动物中,PIWI 相互作用 RNA(piRNA)引导 PIWI 蛋白沉默转座子并调节基因表达。产生 piRNA 的机制据推测在不同的细胞类型、组织和动物中有所不同。相反,我们的数据表明,有一种单一的模型可以解释大多数动物的 piRNA 产生。piRNA 通过引导 PIWI 蛋白切割前体转录本来启动 piRNA 的产生。接下来,PIWI 蛋白指导切割前体转录本的逐步片段化,产生头尾相连的相列前体 piRNA(pre-piRNA)。我们的分析在包括人类在内的广泛进化动物中检测到了这种 piRNA 生物发生策略的证据。因此,PIWI 蛋白通过相同的机制在最后共同祖先早于大多数动物谱系分支的物种中启动和维持 piRNA 生物发生。统一模型将 PIWI 家族 Argonautes 置于 piRNA 生物学的中心,并表明祖动物——Urmetazoan——既使用 PIWI 蛋白生成 piRNA 向导,又执行 piRNA 功能。