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The regulation of mammalian maternal-to-embryonic transition by Eukaryotic translation initiation factor 4E

By Yan Li, Xuefeng Huang, Jianan Tang, Xu Ji, Miao Liu, Lu Chang, Jing Liu, Yihua Gu, Changgen Shi, Wuhua Ni, Hui-juan Shi, Chris O’Neill, Xingliang Jin

Posted 16 Jan 2020
bioRxiv DOI: 10.1101/2020.01.16.908582

Genetic and inhibitor studies show expression of eukaryotic translation initiation factor 4E (eIF4E) was required for the successful maternal-to-embryonic transition of mouse embryos. eIF4E was in both gametes and in the cytoplasm and pro-nuclei soon after fertilization, and at each stage of early development. Knockout (Eif4e-/-) by PiggyBac (PB) [Act-RFP] transposition caused peri-implantation embryonic lethality due to the failure of embryos to form a pluripotent epiblast. Maternal stores of eIF4E supported development up to the 2-4-cell stage after which new expression occurred from both alleles. Inhibition of the maternally acquired stores of eIF4E (4EGI-1 inhibitor) resulted in a developmental block at the 2-4-cell stage. 4E-BP1 is a hypophosphorylation-dependent negative regulator of eIF4E. mTOR activity was required for 4E-BP1 phosphorylation and inhibiting 4EGI-1 retarded embryo development. eIF4E expression and activity is regulated at key embryonic transitions in the mammalian embryo and is essential for successful transition to embryonic control of development.

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