Retrotransposon LINE-1 bodies in the cytoplasm of piRNA-deficient mouse spermatocytes: Ribonucleoproteins overcoming the integrated stress response.
Retrotransposon LINE-1 bodies in the cytoplasm of piRNA-deficient mouse spermatocytes: Ribonucleoproteins overcoming the integrated stress response.
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DOI：
10.1371/journal.pgen.1010797
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发表时间：
2023-06
期刊：
影响因子：
4.5
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中科院分区：
文献类型：
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转座元件(Te)是一种可移动的DNA序列，其过度增殖会危及宿主。尽管动物已经进化出了强大的TE靶向防御系统，包括Piwi相互作用(Pi)RNA，反转录转座子LINE-1(L1)仍然在人类和小鼠中蓬勃发展。为了深入了解L1的耐力，我们研究了PiRNA缺陷的大漩涡缺失小鼠生殖细胞中的L1小体(LBS)和ORF1p复合体。我们报告了ORF1p与TE RNAs、基因mRNAs和应激颗粒蛋白的相互作用，这与早期的研究一致。我们还发现ORF1p与CCR4-非死烯基化复合体和PRKRA有关，PRKRA是一种蛋白激酶R因子。尽管ORF1p与这些RNA表达的负调控因子相互作用，但LB定位的mRNAs的稳定性和翻译保持不变。为了仔细研究这些发现，我们研究了PRKRA对培养细胞中L1的影响，结果表明它提高了ORF1p水平和L1逆转录转座。这些结果表明，ORF1p驱动的凝聚体促进了L1的繁殖，而不影响内源RNA的代谢。转座元件(TES)是一种可移动的DNA序列，其增殖危及宿主细胞及其基因组的完整性。尽管细胞已经获得了复杂的TE靶向防御，但TES继续在所有生命形式中蓬勃发展。为了解决这个令人着迷的问题，这项研究重点研究了一种特殊类型的TE，即逆转座子LINE-1。这项工作表明，表达LINE-1的小鼠生殖细胞产生富含LINE-1、RNA和与RNA表达负调控有关的蛋白质的细胞质聚集体(LINE-1小体或LBS)。尽管LBS具有压倒性的抑制性质，但Lb定位的RNA的完整性和翻译不受影响。RNA的表达似乎保持完整，因为LINE-1已经适应了与PRKRA蛋白的相互作用，PRKRA蛋白将胁迫信号传递给下游蛋白，引发普遍的翻译抑制。事实上，LINE-1和PRKRA在培养细胞中的同时表达提高了LINE-1蛋白的表达和动员。我们的数据表明，LINE-1已经进化出一种机制来抵消翻译关闭，从而在不损害宿主细胞的情况下增加了它的繁殖机会。
Transposable elements (TE) are mobile DNA sequences whose excessive proliferation endangers the host. Although animals have evolved robust TE-targeting defenses, including Piwi-interacting (pi)RNAs, retrotransposon LINE-1 (L1) still thrives in humans and mice. To gain insights into L1 endurance, we characterized L1 Bodies (LBs) and ORF1p complexes in germ cells of piRNA-deficient Maelstrom null mice. We report that ORF1p interacts with TE RNAs, genic mRNAs, and stress granule proteins, consistent with earlier studies. We also show that ORF1p associates with the CCR4-NOT deadenylation complex and PRKRA, a Protein Kinase R factor. Despite ORF1p interactions with these negative regulators of RNA expression, the stability and translation of LB-localized mRNAs remain unchanged. To scrutinize these findings, we studied the effects of PRKRA on L1 in cultured cells and showed that it elevates ORF1p levels and L1 retrotransposition. These results suggest that ORF1p-driven condensates promote L1 propagation, without affecting the metabolism of endogenous RNAs. Transposable elements (TEs) are mobile DNA sequences whose proliferation endangers the integrity of the host cell and its genome. Although cells have acquired sophisticated TE-targeting defenses, TEs continue to thrive in all life forms. To address this fascinating question, this study focused on a particular type of TE known as retrotransposon LINE-1. This work shows that LINE-1-expressing germ cells of mice develop cytoplasmic aggregates (LINE-1 bodies or LBs) enriched in LINE-1, RNAs, and proteins implicated in the negative regulation of RNA expression. Despite the overwhelming repressive nature of LBs, the integrity and translation of LB-localized RNAs are not affected. RNA expression appears to stay intact because LINE-1 has adapted to interact with the PRKRA protein that relays stress signals to downstream proteins, triggering general translational inhibition. Indeed, the simultaneous expression of LINE-1 and PRKRA in cultured cells elevates LINE-1 protein expression and mobilization. Our data suggest that LINE-1 has evolved a mechanism to counteract the translational shut-off, thus increasing its chances of propagation without compromising the host cell.
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影响因子：
30.8
作者：
Dewannieux, M;Esnault, C;Heidmann, T
通讯作者：
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