Comprehensive maturity of nuclear pore complexes regulates zygotic genome activation

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.

Automated summary

Nuclear pore complexes (NPCs) serve as channels for nucleocytoplasmic transport, and their maturity plays a crucial role in the onset of gene activation in early zebrafish embryogenesis. NPCs increase in size and complexity with development, and more nucleoporin proteins are recruited and assembled into NPCs. This affects the nuclear transport of maternal transcription factors, ultimately influencing the activation of zygotic genes.