Homeostatic regulation of nucleoporins is a central driver of nuclear pore biogenesis.

ABSTRACT: Nuclear pore complexes (NPCs) are channels that control access to the genome. The number of NPCs that cells assemble varies between different cell types and in disease. However, the mechanisms regulating NPC formation in mammalian cells remain unclear. Using a genome-wide small interfering RNA (siRNA) screen, we identify translation-related factors, proteasome components, and the CCR4-NOT complex as top regulators of NPC assembly and numbers. While inhibition of ribosomal function and protein translation reduces NPC formation, blocking protein degradation or CCR4-NOT function increases NPC numbers. We demonstrate that CCR4-NOT inhibition raises global mRNA levels, increasing the pool of nucleoporin mRNAs available for translation. Upregulation of nucleoporin complexes in CCR4-NOT-inhibited

SUBMITTER: Sakuma S 

PROVIDER: S-EPMC12080372 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature