德国马克斯·普朗克分子遗传学研究所Stefan Mundlos小组的研究认为LTR逆转录转座子采用增强子产生病毒样颗粒，导致发育肢体表型。相关论文于2025年7月9日发表于国际顶尖学术期刊《自然—遗传学》杂志上。

在这里，该团队发现TE插入可以采用附近的调节活性，导致产生影响胚胎形成的细胞类型特异性病毒样颗粒（VLP）。未能沉默插入Fgf8基因上游的LTR反转录转座子，导致它们在小鼠发育过程中共表达。VLP在发育肢体中表达Fgf8的细胞中组装引发凋亡细胞死亡，导致肢体畸形，类似于人的指外畸形。这种表型可以通过突变反转录转座子编码序列来拯救，从而阻止其完整的内源性逆转录病毒周期。他们的发现阐明了TE插入可以被纳入局部基因组调控景观，并且着床后胚胎中VLP的产生可以引起发育缺陷。

据了解，转座因子（TE）分布在哺乳动物基因组中。TE的沉默可以防止由导致基因组不稳定的全局激活或干扰基因转录的插入突变引起的有害影响。然而，TE的激活是否能在不直接影响基因表达的情况下抑制疾病在很大程度上是未知的。

附：英文原文

Title: Enhancer adoption by an LTR retrotransposon generates viral-like particles, causing developmental limb phenotypes

Author: Glaser, Juliane, Cova, Giulia, Fauler, Beatrix, Prada-Medina, Cesar A., Stanislas, Virginie, Phan, Mai H. Q., Schpflin, Robert, Aktas, Yasmin, Franke, Martin, Andrey, Guillaume, Bartzoka, Natalia, Paliou, Christina, Laupert, Verena, Chan, Wing-Lee, Wittler, Lars, Mielke, Thorsten, Mundlos, Stefan

Issue&Volume: 2025-07-09

Abstract: Transposable elements (TEs) are scattered across mammalian genomes. Silencing of TEs prevents harmful effects caused by either global activation leading to genome instability or insertional mutations disturbing gene transcription. However, whether the activation of a TE can cause disease without directly affecting gene expression is largely unknown. Here we show that a TE insertion can adopt nearby regulatory activity, resulting in the production of cell-type-specific viral-like particles (VLPs) that affect embryo formation. Failure to silence an LTR retrotransposon inserted upstream of the Fgf8 gene results in their co-expression during mouse development. VLP assembly in the Fgf8-expressing cells of the developing limb triggers apoptotic cell death, resulting in a limb malformation resembling human ectrodactyly. The phenotype can be rescued by mutating the retrotransposon coding sequence, thus preventing its full endogenous retroviral cycle. Our findings illustrate that TE insertions can be incorporated into the local genomic regulatory landscape and that VLP production in post-implantation embryos can cause developmental defects.

DOI: 10.1038/s41588-025-02248-5

Source: https://www.nature.com/articles/s41588-025-02248-5