Transposable elements can drive genome evolution, but their enhanced activity is detrimental to the host and therefore must be tightly regulated. The Piwi-interacting small RNA (piRNA) pathway is vital for the regulation of transposable elements, by inducing transcriptional silencing or post-transcriptional decay of mRNAs. Here we show that piRNAs and piRNA biogenesis components regulate precursor mRNA splicing of P-transposable element transcripts in vivo, leading to the production of the non-transposase-encoding mature mRNA isoform in Drosophila germ cells. Unexpectedly, we show that the piRNA pathway components do not act to reduce transcript levels of the P-element transposon during P–M hybrid dysgenesis, a syndrome that affects germline development in Drosophila. Instead, splicing regulation is mechanistically achieved together with piRNA-mediated changes to repressive chromatin states, and relies on the function of the Piwi–piRNA complex proteins Asterix (also known as Gtsf1) and Panoramix (Silencio), as well as Heterochromatin protein 1a (HP1a; encoded by Su(var)205). Furthermore, we show that this machinery, together with the piRNA Flamenco cluster, not only controls the accumulation of Gypsy retrotransposon transcripts but also regulates the splicing of Gypsy mRNAs in cultured ovarian somatic cells, a process required for the production of infectious particles that can lead to heritable transposition events. Our findings identify splicing regulation as a new role and essential function for the Piwi pathway in protecting the genome against transposon mobility, and provide a model system for studying the role of chromatin structure in modulating alternative splicing during development.

中文翻译：

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piRNA 介导的体细胞和种系中转座子选择性剪接的调节

转座因子可以驱动基因组进化，但它们增强的活性对宿主有害，因此必须受到严格监管。Piwi 相互作用小 RNA (piRNA) 通路通过诱导 mRNA 的转录沉默或转录后衰变对转座因子的调节至关重要。在这里，我们表明 piRNA 和 piRNA 生物发生成分在体内调节 P 转座元件转录物的前体 mRNA 剪接，导致在果蝇生殖细胞中产生非转座酶编码的成熟 mRNA 同种型。出乎意料的是，我们发现 piRNA 通路组分在 P-M 杂种发育不全（一种影响果蝇种系发育的综合征）期间不会降低 P 元件转座子的转录水平。反而，剪接调控与 piRNA 介导的染色质抑制状态变化一起在机械上实现，并依赖于 Piwi-piRNA 复合蛋白 Asterix（也称为 Gtsf1）和 Panoramix（Silencio）以及异染色质蛋白 1a（HP1a；由 Su(var)205 编码）。此外，我们表明，这种机制与 piRNA Flamenco 簇一起，不仅控制 Gypsy 逆转录转座子转录本的积累，而且还调节培养的卵巢体细胞中 Gypsy mRNA 的剪接，这是产生感染性颗粒所需的过程，可导致到可遗传的转座事件。我们的研究结果将剪接调节确定为 Piwi 通路在保护基因组免受转座子迁移方面的新作用和基本功能，