Institut de Génétique Humaine, CNRS, 34396 Montpellier CEDEX 5, France.
Genome Res. 2012 Oct;22(10):1877-88. doi: 10.1101/gr.136614.111. Epub 2012 May 3.
The maintenance of genome integrity is an essential trait to the successful transmission of genetic information. In animal germ cells, piRNAs guide PIWI proteins to silence transposable elements (TEs) in order to maintain genome integrity. In insects, most TE silencing in the germline is achieved by secondary piRNAs that are produced by a feed-forward loop (the ping-pong cycle), which requires the piRNA-directed cleavage of two types of RNAs: mRNAs of functional euchromatic TEs and heterochromatic transcripts that contain defective TE sequences. The first cleavage that initiates such an amplification loop remains poorly understood. Taking advantage of the existence of strains that are devoid of functional copies of the LINE-like I-element, we report here that in such Drosophila ovaries, the initiation of a ping-pong cycle is exclusively achieved by secondary I-element piRNAs that are produced in the ovary and deposited in the embryonic germline. This unusual secondary piRNA biogenesis, detected in the absence of functional I-element copies, results from the processing of sense and antisense transcripts of several different defective I-element. Once acquired, for instance after ancestor aging, this capacity to produce heterochromatic-only secondary piRNAs is partially transmitted through generations via maternal piRNAs. Furthermore, such piRNAs acting as ping-pong initiators in a chromatin-independent manner confer to the progeny a high capacity to repress the I-element mobility. Our study explains, at the molecular level, the basis for epigenetic memory of maternal immunity that protects females from hybrid dysgenesis caused by transposition of paternally inherited functional I-element.
基因组完整性的维持是成功传递遗传信息的必要特征。在动物生殖细胞中，piRNA 指导 PIWI 蛋白沉默转座元件 (TE)，以维持基因组完整性。在昆虫中，大多数生殖细胞中的 TE 沉默是通过由正反馈环（乒乓循环）产生的二级 piRNA 实现的，这需要 piRNA 指导对两种类型的 RNA 的切割：功能常染色质 TE 的 mRNA 和含有缺陷 TE 序列的异染色质转录本。启动这种扩增环的第一次切割仍然知之甚少。利用缺乏功能拷贝的 LINE 样 I 元件的菌株的存在，我们在这里报告，在这些果蝇卵巢中，乒乓循环的启动仅由在卵巢中产生并沉积在胚胎生殖细胞中的二级 I 元件 piRNA 实现。这种在缺乏功能 I 元件拷贝的情况下检测到的异常二级 piRNA 生物发生，是由几个不同缺陷 I 元件的 sense 和 antisense 转录本的加工产生的。一旦获得，例如在祖先衰老之后，这种产生仅异染色质的次级 piRNA 的能力通过母系 piRNA 在几代人中部分传递。此外，这种以非染色质依赖方式作为乒乓启动子的 piRNA 赋予后代抑制 I 元件移动的高能力。我们的研究从分子水平解释了母体免疫的表观遗传记忆的基础，该记忆保护雌性免受由父系遗传功能 I 元件转座引起的杂种不育。
