MIWI2 and MILI Have Differential Effects on piRNA Biogenesis and DNA Methylation.
MIWI2 and MILI Have Differential Effects on piRNA Biogenesis and DNA Methylation.
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DOI：
10.1016/j.celrep.2015.07.036
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发表时间：
2015-08-25
期刊：
影响因子：
8.8
通讯作者：
Aravin AA
中科院分区：
文献类型：
--
作者：
Manakov SA;Pezic D;Marinov GK;Pastor WA;Sachidanandam R;Aravin AA
在发育雄性生殖细胞、精原细胞时，两种 Piwi 蛋白 MILI 和 MIWI2 使用 Piwi 相互作用 RNA (piRNA) 向导来抑制转座元件 (TE) 表达并确保基因组稳定性和正确的配子发生。除了在转录后 TE 抑制中发挥作用外，这两种蛋白也是 TE 序列 DNA 甲基化所必需的。在这里，我们分析了 Miwi2 缺陷对 piRNA 生物合成和转座子抑制的影响。 Miwi2 缺陷对 piRNA 生物发生仅产生很小的影响；然而，Miwi2 敲除小鼠的 piRNA 谱表明，几个 LINE1 TE 家族过度表达，导致乒乓 piRNA 循环激活。此外，我们发现 MILI 和 MIWI2 在细胞核内的 TE 抑制中具有不同的功能。 MILI 负责比 MIWI2 更大的 TE 家族子集的 DNA 甲基化，这表明这些蛋白质在建立 DNA 甲基化模式中具有独立的作用。
In developing male germ cells, prospermatogonia, two Piwi proteins, MILI and MIWI2, use Piwi-interacting RNA (piRNA) guides to repress transposable element (TE) expression and ensure genome stability and proper gametogenesis. In addition to their roles in post-transcriptional TE repression, both proteins are required for DNA methylation of TE sequences. Here, we analyzed the effect of Miwi2 deficiency on piRNA biogenesis and transposon repression. Miwi2 deficiency had only a minor impact on piRNA biogenesis; however, the piRNA profile of Miwi2-knockout mice indicated overexpression of several LINE1 TE families that led to activation of the ping-pong piRNA cycle. Furthermore, we found that MILI and MIWI2 have distinct functions in TE repression in the nucleus. MILI is responsible for DNA methylation of a larger subset of TE families than MIWI2 is, suggesting that the proteins have independent roles in establishing DNA methylation patterns.