Hijacking Oogenesis Enables Massive Propagation of LINE and Retroviral Transposons.
Hijacking Oogenesis Enables Massive Propagation of LINE and Retroviral Transposons.
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劫持卵子发生使 LINE 和逆转录病毒转座子能够大规模传播。
DOI：
10.1016/j.cell.2018.06.040
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发表时间：
2018
期刊：
影响因子：
64.5
通讯作者：
Zhang,ZzZhao
中科院分区：
文献类型：
--
作者：
Wang,Lu;Dou,Kun;Moon,Sungjin;Tan,FrederickJ;Zhang,ZzZhao
尽管动物已经进化出多种机制来抑制转座子，但导致突变和疾病的“泄漏”动员仍在发生。这表明转座子使用特定的策略来实现稳健的传播。通过直接跟踪动员，我们表明，在卵子发生的短而特定的时间窗内，反转录转座子通过细胞类型特异性的靶向策略实现大规模扩增。反转录转座子很少在未分化的生殖系干细胞中移动。然而，随着卵子发生的进行，它们利用高度多倍体的支持哺育细胞作为工厂，大量制造入侵产品。此外，反转录转座子本身很少整合到哺乳细胞中，而是通过微管介导的运输，优先靶向相互连接的卵母细胞的DNA。阻断来自哺育细胞的微管依赖的细胞间运输显著减轻对卵母细胞基因组的损害。我们的数据显示，寄生基因组元素可以有效地劫持宿主的发育过程，使其强劲繁殖，从而推动进化变化并引发疾病。
Although animals have evolved multiple mechanisms to suppress transposons, "leaky" mobilizations that cause mutations and diseases still occur. This suggests that transposons employ specific tactics to accomplish robust propagation. By directly tracking mobilization, we show that, during a short and specific time window of oogenesis, retrotransposons achieve massive amplification via a cell-type-specific targeting strategy. Retrotransposons rarely mobilize in undifferentiated germline stem cells. However, as oogenesis proceeds, they utilize supporting nurse cells—which are highly polyploid and eventually undergo apoptosis—as factories to massively manufacture invading products. Moreover, retrotransposons rarely integrate into nurse cells themselves but, instead, via microtubule-mediated transport, they preferentially target the DNA of the interconnected oocytes. Blocking microtubule-dependent intercellular transport from nurse cells significantly alleviates damage to the oocyte genome. Our data reveal that parasitic genomic elements can efficiently hijack a host developmental process to propagate robustly, thereby driving evolutionary change and causing disease.