本期文章：《自然》：Online/在线发表

澳大利亚加文医学研究所Cecile King研究小组发现，逆转座元件Lx9对病毒感染的免疫反应起刹车作用。该研究于2022年8月10日在线发表于国际一流学术期刊《自然》。

研究人员表明，CRISPR-Cas9介导的可转座元件（即LINE-1逆转录转座子Lx9c11）在小鼠中的删除导致了对病毒感染的夸张和致命的免疫反应。Lx9c11对一种非编码RNA（Lx9c11-RegoS）的新生至关重要，这种RNA能调节Schlafen家族的基因，减少高炎症表型并挽救病毒感染的Lx9c11^-/-小鼠的死亡。这些发现提供了证据，证明可转座元件可以控制免疫系统，从而利于病毒感染期间的宿主生存。

据悉，六十多年前，人们就提出了被称为可转座元件的核酸移动单位可以作为基因组控制元件的概念。然而，直到基因组测序技术的发展才揭示了可转座元件的丰度和种类，现在已知它们占哺乳动物基因组的三分之二。可转座元件中存在的DNA调控区域包括启动子、增强子和转录因子结合位点，这导致了一个假设，即可转座元件已被用来调节哺乳动物基因表达和细胞表型。哺乳动物的可转座元件包括最近获得的和古代的可转座元件，它们在进化过程中一直保持在基因组中。古代保守的可转座元件的存在与调控功能的可能性呈正相关，但功能验证仍然是确定对适应性有积极影响的可转座元件插入的必要步骤。

附：英文原文

Title: The retroelement Lx9 puts a brake on the immune response to virus infection

Author: Bartonicek, Nenad, Rouet, Romain, Warren, Joanna, Loetsch, Claudia, Rodriguez, Gabriela Santos, Walters, Stacey, Lin, Francis, Zahra, David, Blackburn, James, Hammond, Jillian M., Reis, Andre L. M., Deveson, Ira W., Zammit, Nathan, Zeraati, Mahdi, Grey, Shane, Christ, Daniel, Mattick, John S., Chtanova, Tatyana, Brink, Robert, Dinger, Marcel E., Weatheritt, Robert J., Sprent, Jonathan, King, Cecile

Issue&Volume: 2022-08-10

Abstract: The notion that mobile units of nucleic acid known as transposable elements can operate as genomic controlling elements was put forward over six decades ago1,2. 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 genomes3,4. The presence of DNA regulatory regions including promoters, enhancers and transcription-factor-binding sites within transposable elements5,6,7,8 has led to the hypothesis that transposable elements have been co-opted to regulate mammalian gene expression and cell phenotype8,9,10,11,12,13,14. 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.

DOI: 10.1038/s41586-022-05054-9