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Learn MoreThe nuclear exosome targeting (NEXT) complex is responsible for recruiting RNA exosomes to degrade specific nuclear RNAs in mammalian cells. However, its function in mammalian development remains unknown. Here, we found that the depletion of a central factor of the NEXT complex, Zcchc8, resulted in mouse developmental defects, a shortened life span and infertility. Zcchc8-deficient embryonic stem cells (ESCs) exhibited proliferation abnormalities and reduced developmental potencies. Interestingly, we found that retrotransposon elements, especially LINE1 RNAs, are targeted and degraded by Zcchc8 in ESCs. We subsequently demonstrated that Zcchc8-depleted oocytes show defects in meiotic maturation and early embryo development. Moreover, the sustained expression of higher levels of LINE1 RNA was also detected in maternal Zcchc8-depleted oocytes and Zcchc8-deficient embryos, which can further increase chromatin accessibility. Collectively, our study uncovers the important role of Zcchc8 in the degradation of LINE1 transcripts in early embryos and ESCs at the posttranscriptional level. SOURCE: You Wu (wuyou@tongji.edu.cn) - tongji university
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