Regulation of RNA fluxes by the NuA4 acetyl-transferase complex – NumREx

NuA4 is an evolutionary conserved lysine-acetyltransferase complex that plays important roles in gene expression, by creating a favorable chromatin environment for transcription. The coordinating team found that in budding yeast, NuA4 also promotes the nuclear export of mRNA. NuA4-dependent mRNA export promotes the G1/S transition in yeast mother cells and is inhibited in daughter cells by the deacetylase Hos3, to prevent premature entry into S-phase until daughters reach a critical cell size. Yeast NuA4 promotes mRNA export by acetylation of Nuclear Pore Complexes, which mediate transport of mRNAs to the cytoplasm. Furthermore, preliminary data reveal that NuA4 is also involved in mRNA export in mouse embryonic stem cells. These results uncover a novel, conserved role for NuA4 in controlling gene expression dually, at the level of both transcription and mRNA export. This proposal aims to establish the molecular mechanism by which NuA4 promotes selective mRNA export in yeast and embryonic stem cells, using genetics, imaging, and genomics approaches.