Investigating the mechanisms and impact of nuclear pore-associated translation – TRANSLAPORES

In eukaryotic cells, asymmetrical mRNA localization and site-specific translation have emerged as universal strategies to regulate gene expression and define the specific proteome of intracellular compartments. While proteins were believed to enter the nucleus through nuclear pore complexes (NPCs) in a post-translational manner, a collaborative study between the French and the Swiss applicants has instead recently led to the discovery of a subset of mRNAs translated at the vicinity of the nuclear envelope in the yeast S. cerevisiae. Based on unique preliminary results and dedicated approaches gathered by both partner laboratories, this project thus aims to investigate the mechanisms and the cellular impact of nuclear pore-associated translation. In this respect, systematic strategies will be used to expand the repertoire of mRNAs translated at NPCs, and combined with reporter-based approaches to decipher the cis- and trans-acting mechanisms underlying localized translation. State-of-the-art single molecule mRNA imaging and targeted ribosome profiling will be further employed to investigate the spatio-temporal dynamics of translation at NPCs and its regulation in multiple physiological or stress situations. A panel of genetics, biochemistry and imaging methods will finally tackle the physiological relevance of NPC-associated translation, especially regarding the maintenance of cellular proteostasis and the assembly of nuclear pores. By building on the complementary expertise of the applicants in NPC biology and translational processes, this project is thereby expected to shed light on an emerging field of research.