The piRNA Response to Retroviral Invasion of the Koala Genome

Antisense piRNAs guide silencing of established transposons during germline development, and sense piRNAs drive ping-pong amplification of the antisense pool, but how the germline responds to genome invasion is not understood. The KoRV-A gammaretrovirus infects the soma and germline and is sweeping through wild koalas by a combination of horizontal and vertical transfer, allowing direct analysis of retroviral invasion of the germline genome. Gammaretroviruses produce spliced Env mRNAs and unspliced transcripts encoding Gag, Pol and the viral genome, but KoRV-A piRNAs are almost exclusively derived from unspliced genomic transcripts and are strongly sense strand biased. Significantly, selective piRNA processing of unspliced proviral transcripts is conserved from insects to placental mammals. We speculate that bypassed splicing generates a conserved molecular pattern that directs proviral genomic transcripts to the piRNA biogenesis machinery, and that this "innate" piRNA response suppresses transposition until antisense piRNAs are produced, establishing sequence-specific adaptive immunity. DNAseq, RNAseq and small RNAseq data for koala testes, livers and brains; RNAseq and small RNAseq data for different strains of mouse.反义piRNA（Piwi-interacting RNA）在生殖系发育过程中介导已整合转座子的沉默，而有义piRNA则推动反义piRNA池的乒乓扩增，但生殖系如何响应基因组入侵的分子机制仍未阐明。KoRV-A γ逆转录病毒（gammaretrovirus）可感染体细胞与生殖系，并通过水平传播与垂直传播的联合方式在野生考拉种群中快速扩散，这为直接研究逆转录病毒入侵生殖系基因组的过程提供了绝佳的研究模型。γ逆转录病毒会产生剪接后的Env mRNA以及编码Gag、Pol与病毒基因组的未剪接转录本，但KoRV-A相关piRNA几乎全部源自未剪接的基因组转录本，且呈现强烈的有义链偏好性。值得注意的是，对未剪接前病毒转录本的选择性piRNA加工机制在昆虫到胎盘类哺乳动物中均保守存在。我们推测，未经历剪接的转录本会形成一种保守的分子模式，引导前病毒基因组转录本进入piRNA生成通路，而这种‘先天’piRNA应答会抑制转座过程，直至反义piRNA产生，从而建立序列特异性的适应性免疫。本数据集包含考拉睾丸、肝脏与脑组织的DNA测序（DNAseq）、RNA测序（RNAseq）以及小RNA测序（small RNAseq）数据，以及不同品系小鼠的RNA测序与小RNA测序数据。