细胞生物学
生物
胚胎干细胞
核糖核酸
外小体复合体
胚胎发生
胚胎
外体
转录因子
同源盒蛋白纳米
遗传学
微泡
非编码RNA
诱导多能干细胞
小RNA
基因
作者
You Wu,Wenqiang Liu,Jiayu Chen,Shuaitong Liu,Mingzhu Wang,Lei Yang,Chuan Chen,Meijie Qi,Yiwen Xu,Zhibin Qiao,Rushuang Yan,Xiaochen Kou,Yanhong Zhao,Bin Shen,Jie Yin,Hong Wang,Yawei Gao,Shaorong Gao
出处
期刊:Cell Reports
[Elsevier]
日期:2019-11-01
卷期号:29 (8): 2461-2472.e6
被引量:28
标识
DOI:10.1016/j.celrep.2019.10.055
摘要
Summary
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.
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