UBAP2L drives scaffold assembly of nuclear pore complexes at the intact nuclear envelope

Yongrong Liao (1, 2) , Leonid Andronov (3) , Xiaotian Liu (2) , Junyan Lin (2) , Lucile Guerber (2) , Linjie Lu (1, 2) , Arantxa Agote-Arán (2) , Evanthia Pangou (2, 1) , Li Ran (2) , Charlotte Kleiss (2, 1) , Mengdi Qu (2) , Stephane Schmucker (2) , Luca Cirillo (4, 5) , Zhirong Zhang (2) , Daniel Riveline (2) , Monica Gotta (6, 4) , Bruno Klaholz (2) , Izabela Sumara (2)

1 IGBMC - Institut de génétique et biologie moléculaire et cellulaire
2 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
3 Inserm U964 - CNRS UMR7104 - IGBMC - Centre for Integrative Biology - CBI
4 Department of Cellular Physiology and Metabolism
5 UNIGE - Université de Genève = University of Geneva
6 NCCR-Chemical Biology - Swiss National Centre for Competence in Research Programme Chemical Biology

Abstract Assembly of macromolecular complexes at correct cellular sites is crucial for cell function. Nuclear pore complexes (NPCs) are large cylindrical assemblies with eightfold rotational symmetry, built through hierarchical binding of nucleoporins (Nups) forming distinct subcomplexes. Here, we uncover a direct role of ubiquitin-associated protein 2-like (UBAP2L) in the biogenesis of properly organized and functional NPCs at the intact nuclear envelope (NE) in human cells. UBAP2L localizes to the nuclear pores and drives the formation of the Y-complex, an essential scaffold component of the NPC, and its localization to the NE. UBAP2L facilitates the interaction of the Y-complex with POM121 and Nup153, the critical upstream factors in a well-defined sequential order of Nups assembly onto NE during interphase. Timely localization of the cytoplasmic Nup transport factor fragile X-related protein 1 (FXR1) to the NE and its interaction with the Y-complex are likewise dependent on UBAP2L. Thus, this NPC biogenesis mechanism integrates the cytoplasmic and the nuclear NPC assembly signals and ensures efficient nuclear transport, adaptation to nutrient stress and cellular proliferative capacity, highlighting the importance of NPC homeostasis at the intact nuclear envelope. Teaser Liao et al. show how UBAP2L drives the assembly of the scaffold elements into symmetrical and functional NPCs at the nuclear envelope in human cells.

Domaines: Sciences du Vivant [q-bio]

Yongrong Liao, Leonid Andronov, Xiaotian Liu, Junyan Lin, Lucile Guerber, et al.. UBAP2L drives scaffold assembly of nuclear pore complexes at the intact nuclear envelope. 2023. ⟨hal-04247644⟩