Germline piRNAs counteract endogenous retrovirus invasion from somatic cells

In metazoan gonads, transposable elements (TEs) mobilization is limited by PIWI-interacting RNAs (piRNAs). These small RNAs originate from specific source loci, the piRNA clusters. piRNAs are known to silence TEs in the cells where they are produced. Endogenous retroviruses (ERVs), a subclass of TEs, pose a particular threat because they are capable of transiting from cell to cell. In this study, we reveal that piRNAs produced locally in germ cells counteract invasion by ERVs arriving from adjacent somatic cells. We reactivated the Drosophila ERVZAMin somatic gonadal cells by deleting, using CRISPR-Cas9 genome editing, its single copy in the somaticflamencopiRNA cluster, while keeping the piRNA pathway fully functional. Upon reactivation,ZAMinvaded the oocytes, resulting in transposition and severe fertility defects. We show that onceZAM-piRNAs are produced in germ cells they counter the invasion. Our study sheds new light on the mechanisms of recognition and regulation of invasive genetic elements, which is essential for the maintenance of genome integrity. Overall design: RNA sequencing

在后生动物性腺中，转座因子（transposable elements，TEs）的转座活动受PIWI互作RNA（PIWI-interacting RNAs，piRNAs）的限制。这类小型RNA起源于特定的源位点——piRNA簇。已知piRNAs可在其产生的细胞中沉默转座因子。作为转座因子的一个子类，内源性逆转录病毒（endogenous retroviruses，ERVs）构成了特殊威胁，因其能够在细胞间传播。本研究揭示，生殖细胞局部产生的piRNAs可抵御来自邻近体细胞的内源性逆转录病毒侵袭。我们通过CRISPR-Cas9基因组编辑技术，敲除了体细胞性腺细胞中单个拷贝的果蝇ZAM内源性逆转录病毒所在的体细胞flamenco piRNA簇，同时保持piRNA通路完全正常运作，从而重新激活了该病毒。重新激活后，ZAM侵袭卵母细胞，引发转座并导致严重的生育缺陷。研究表明，一旦生殖细胞产生ZAM-piRNAs，便可对抗该病毒的侵袭。本研究为侵袭性遗传因子的识别与调控机制提供了新见解，这对维持基因组完整性至关重要。整体实验设计：RNA测序