RNase H2, mutated in Aicardi-Goutières syndrome, promotes LINE-1 retrotransposition.
RNase H2, mutated in Aicardi-Goutières syndrome, promotes LINE-1 retrotransposition.
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在Aicardi-Goutières综合征中突变的RNase H2促进了LINE-1逆转录位。
DOI：
10.15252/embj.201798506
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发表时间：
2018-08-01
期刊：
影响因子：
--
通讯作者：
Garcia-Perez JL
中科院分区：
文献类型：
--
作者：
Benitez-Guijarro M;Lopez-Ruiz C;Tarnauskaitė Ž;Murina O;Mian Mohammad M;Williams TC;Fluteau A;Sanchez L;Vilar-Astasio R;Garcia-Canadas M;Cano D;Kempen MH;Sanchez-Pozo A;Heras SR;Jackson AP;Reijns MA;Garcia-Perez JL
长插入元件1（LINE‐1）元件是一类在哺乳动物基因组中具有活性的丰富的反转录转座子。平均每个人类基因组包含约100个具有逆转录转座能力的LINE-1，其活性受到细胞阻遏物和激活物的联合作用的影响。TREX 1、SAMHD 1和ADAR 1是已知的LINE-1阻遏物，当突变时会导致自身炎症性疾病AGS。RNase H2的突变是AGS最常见的原因，其活性被认为类似地控制LINE-1逆转录转座。因此，有人认为LINE-1活性增加可能是AGS中异常先天免疫激活的原因。在这里，我们确定，与预期相反，RNase H2是有效的LINE-1逆转录转座所必需的。由于RNase H1过表达部分挽救了RNase H2无效细胞中的缺陷，我们提出了一个模型，其中RNase H2在逆转录后降解LINE-1 RNA，从而完成逆转录转座。这也解释了LINE‐1元件如何在没有自身RNase H活性的情况下有效地逆转录转座。我们的发现似乎与LINE-1衍生的核酸驱动AGS中的自身炎症不一致。
Long INterspersed Element class 1 (LINE‐1) elements are a type of abundant retrotransposons active in mammalian genomes. An average human genome contains ~100 retrotransposition‐competent LINE‐1s, whose activity is influenced by the combined action of cellular repressors and activators. TREX1, SAMHD1 and ADAR1 are known LINE‐1 repressors and when mutated cause the autoinflammatory disorder Aicardi‐Goutières syndrome (AGS). Mutations in RNase H2 are the most common cause of AGS, and its activity was proposed to similarly control LINE‐1 retrotransposition. It has therefore been suggested that increased LINE‐1 activity may be the cause of aberrant innate immune activation in AGS. Here, we establish that, contrary to expectations, RNase H2 is required for efficient LINE‐1 retrotransposition. As RNase H1 overexpression partially rescues the defect in RNase H2 null cells, we propose a model in which RNase H2 degrades the LINE‐1 RNA after reverse transcription, allowing retrotransposition to be completed. This also explains how LINE‐1 elements can retrotranspose efficiently without their own RNase H activity. Our findings appear to be at odds with LINE‐1‐derived nucleic acids driving autoinflammation in AGS.
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影响因子：
14.9
作者：
Chon H;Sparks JL;Rychlik M;Nowotny M;Burgers PM;Crouch RJ;Cerritelli SM
通讯作者：
Cerritelli SM
影响因子：
5.3
作者：
Dmitriev, Sergey E.;Andreev, Dmitri E.;Shatsky, Ivan N.
通讯作者：
Shatsky, Ivan N.
DOI：
10.1073/pnas.0831042100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Brouha, B;Schustak, J;Kazazian, HH
通讯作者：
Kazazian, HH
DOI：
10.1073/pnas.1100273108
发表时间：
2011-12-20
影响因子：
11.1
作者：
Coufal, Nicole G.;Luis Garcia-Perez, Jose;Gage, Fred H.
通讯作者：
Gage, Fred H.
影响因子：
14.9
作者：
Esnault, C;Casella, JF;Heidmann, T
通讯作者：
Heidmann, T