1. Comprehensive maturity of nuclear pore complexes regulates zygotic genome activation.
- Author
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Shen, Weimin, Gong, Bo, Xing, Cencan, Zhang, Lin, Sun, Jiawei, Chen, Yuling, Yang, Changmei, Yan, Lu, Chen, Luxi, Yao, Likun, Li, Guangyuan, Deng, Haiteng, Wu, Xiaotong, and Meng, Anming
- Subjects
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NUCLEOCYTOPLASMIC interactions , *CARRIER proteins , *NUCLEAR transport , *GENOMES , *TRANSCRIPTION factors , *EMBRYOLOGY - Abstract
Nuclear pore complexes (NPCs) are channels for nucleocytoplasmic transport of proteins and RNAs. However, it remains unclear whether composition, structure, and permeability of NPCs dynamically change during the cleavage period of vertebrate embryos and affect embryonic development. Here, we report that the comprehensive NPC maturity (CNM) controls the onset of zygotic genome activation (ZGA) during zebrafish early embryogenesis. We show that more nucleoporin proteins are recruited to and assembled into NPCs with development, resulting in progressive increase of NPCs in size and complexity. Maternal transcription factors (TFs) transport into nuclei more efficiently with increasing CNM. Deficiency or dysfunction of Nup133 or Ahctf1/Elys impairs NPC assembly, maternal TFs nuclear transport, and ZGA onset, while nup133 overexpression promotes these processes. Therefore, CNM may act as a molecular timer for ZGA by controlling nuclear transport of maternal TFs that reach nuclear concentration thresholds at a given time to initiate ZGA. [Display omitted] • Maternal TFs cannot transport into nuclei efficiently in embryos before ZGA • Comprehensive NPC maturity gradually increases in embryos at pre-MBT stages • Comprehensive NPC maturity correlates with TF nuclear transport and ZGA • NPC assembly impairment downregulates TF nuclear transport and delays ZGA Experiments in zebrafish indicate that nuclear pore complex (NPC) maturation serves as a molecular timer of zygote genome activation, a key part of the oocyte-to-embryo transition during vertebrate development. Increased size and complexity of NPCs leads to increased nuclear transport of maternal transcription factors, allowing transcription factors to reach thresholds that initiate zygotic genome activation. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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