Nuclear Exosome Targeting Complex Core Factor Zcchc8 Regulates the Degradation of LINE1 RNA in Early Embryos and Embryonic Stem Cells
Nuclear Exosome Targeting Complex Core Factor Zcchc8 Regulates the Degradation of LINE1 RNA in Early Embryos and Embryonic Stem Cells
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核外泌体靶向复合物核心因子 Zcchc8 调节早期胚胎和胚胎干细胞中 LINE1 RNA 的降解
DOI：
10.1016/j.celrep.2019.10.055
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发表时间：
2019-11-19
期刊：
影响因子：
8.8
通讯作者：
Gao, Shaorong
中科院分区：
文献类型：
--
作者：
Wu, You;Liu, Wenqiang;Gao, Shaorong
核外泌体靶向（NEXT）复合物负责哺乳动物细胞中的特异性核RNA降解。然而，它在发育中的作用仍然未知。在这里，我们发现小鼠中NEXT复合体的核心因子Zcchc 8的缺失会导致发育缺陷、寿命缩短和不孕。我们发现，Zcchc8缺陷的胚胎干细胞（ESCs）表现出增殖异常和发育潜能降低。重要的是，反转录转座子元件LINE1的转录物被发现被Zcchc8靶向并通过Zcchc8介导的机制降解。我们进一步发现，在母体Zcchc8缺失的卵母细胞和胚胎中检测到LINE1 RNA的持续高水平表达。Zcchc8缺失的卵母细胞在受精后的减数分裂成熟和胚胎发生中表现出更高的染色质可及性和发育缺陷。总的来说，我们的研究将Zcchc8介导的RNA降解定义为早期胚胎和ESCs中LINE1转录物的重要转录后调节，其在多能性和早期发育中起重要作用。
The nuclear exosome targeting (NEXT) complex is responsible for specific nuclear RNA degradation in mammalian cells. However, its function in development remains unknown. Here, we find that the depletion of a central factor of the NEXT complex, Zcchc8, in mouse results in developmental defects, a shortened lifespan, and infertility. We find that Zcchc8-deficient embryonic stem cells (ESCs) exhibit proliferation abnormalities and reduced developmental potencies. Importantly, the transcripts of retrotransposon element LINE1 are found to be targeted by Zcchc8 and degraded by a Zcchc8-mediated mechanism. We further find that sustained expression of higher levels of LINE1 RNA is detected in maternal Zcchc8-depleted oocytes and embryos. Zcchc8-depleted oocytes show higher chromatin accessibility and developmental defects in both meiotic maturation and embryogenesis after fertilization. Collectively, our study defines Zcchc8-mediated RNA degradation as an important post-transcription regulation of LINE1 transcripts in early embryos and ESCs, which play vital roles in the pluripotency and early development.