Nuclear pore complex acetylation regulates mRNA export and cell cycle commitment in budding yeast.

Autor: Gomar‐Alba, Mercè, Pozharskaia, Vasilisa, Cichocki, Bogdan, Schaal, Celia, Kumar, Arun, Jacquel, Basile, Charvin, Gilles, Igual, J Carlos, Mendoza, Manuel
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Zdroj: EMBO Journal; 8/1/2022, Vol. 41 Issue 15, p1-20, 20p
Abstrakt: Nuclear pore complexes (NPCs) mediate communication between the nucleus and the cytoplasm, and regulate gene expression by interacting with transcription and mRNA export factors. Lysine acetyltransferases (KATs) promote transcription through acetylation of chromatin‐associated proteins. We find that Esa1, the KAT subunit of the yeast NuA4 complex, also acetylates the nuclear pore basket component Nup60 to promote mRNA export. Acetylation of Nup60 recruits the mRNA export factor Sac3, the scaffolding subunit of the Transcription and Export 2 (TREX‐2) complex, to the nuclear basket. The Esa1‐mediated nuclear export of mRNAs in turn promotes entry into S phase, which is inhibited by the Hos3 deacetylase in G1 daughter cells to restrain their premature commitment to a new cell division cycle. This mechanism is not only limited to G1/S‐expressed genes but also inhibits the expression of the nutrient‐regulated GAL1 gene specifically in daughter cells. Overall, these results reveal how acetylation can contribute to the functional plasticity of NPCs in mother and daughter yeast cells. In addition, our work demonstrates dual gene expression regulation by the evolutionarily conserved NuA4 complex, at the level of transcription and at the stage of mRNA export by modifying the nucleoplasmic entrance to nuclear pores. Synopsis: Lysine acetyltransferases (KATs) are known to associate with the nuclear pore complex (NPC), yet their role in regulating gene expression at this location is not fully understood. Here, in addition to regulating transcription, the budding yeast, KAT Esa1 (NuA4 complex), is found to also promote mRNA export. Esa1, the catalytic subunit of the NuA4 complex, acetylates the nuclear pore complex component Nup60Acetylation of Nup60 recruits the TREX‐2 mRNA export complex to the nuclear basketEsa1‐mediated mRNA export in G1 cells promotes their entry into S phaseDeacetylation of Nup60 by the daughter‐cell localized lysine deacetylase Hos3 causes causes displacement of mRNA export complexes and delays the G1/S transition in daughter cells [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index