The notion that mobile units of nucleic acid known as transposable elements can operate as genomic controlling elements was put forward over six decades ago^1,2. However, it was not until the advancement of genomic sequencing technologies that the abundance and repertoire of transposable elements were revealed, and they are now known to constitute up to two-thirds of mammalian genomes^3,4. The presence of DNA regulatory regions including promoters, enhancers and transcription-factor-binding sites within transposable elements^5,6,7,8 has led to the hypothesis that transposable elements have been co-opted to regulate mammalian gene expression and cell phenotype^{8,9,10,11,12,13,14}. Mammalian transposable elements include recent acquisitions and ancient transposable elements that have been maintained in the genome over evolutionary time. The presence of ancient conserved transposable elements correlates positively with the likelihood of a regulatory function, but functional validation remains an essential step to identify transposable element insertions that have a positive effect on fitness. Here we show that CRISPR–Cas9-mediated deletion of a transposable element—namely the LINE-1 retrotransposon Lx9c11—in mice results in an exaggerated and lethal immune response to virus infection. Lx9c11 is critical for the neogenesis of a non-coding RNA (Lx9c11-RegoS) that regulates genes of the Schlafen family, reduces the hyperinflammatory phenotype and rescues lethality in virus-infected Lx9c11^−/− mice. These findings provide evidence that a transposable element can control the immune system to favour host survival during virus infection.

被称为转座因子的核酸移动单元可以作为基因组控制元件运行的概念是在 60 多年前提出的^1,2。然而，直到基因组测序技术的进步，转座因子的丰度和库才被揭示出来，现在已知它们构成了哺乳动物基因组的三分之二^3,4。^{DNA 调控区域的存在，包括启动子、增强子和转座因子5、6、7、8}中的转录因子结合位点，导致假设转座因子已被选为调节哺乳动物基因表达和细胞表型^{8， 9,10,11,12,13,14}. 哺乳动物转座因子包括最近获得的和随着进化时间在基因组中保持的古老转座因子。古代保守转座因子的存在与调节功能的可能性呈正相关，但功能验证仍然是识别对适应度有积极影响的转座因子插入的重要步骤。在这里，我们表明 CRISPR-Cas9 介导的转座因子缺失 - 即 LINE-1 反转录转座子 Lx9c11 - 在小鼠中导致对病毒感染的夸大和致命的免疫反应。Lx9c11 对调节 Schlafen 家族基因的非编码 RNA (Lx9c11-RegoS) 的新生至关重要，减少过度炎症表型并挽救病毒感染的Lx9c11的致死性^-/-老鼠。这些发现提供了证据，表明转座因子可以控制免疫系统，从而在病毒感染期间有利于宿主存活。