ABSTRACTBeyond their canonical function in nucleocytoplasmic exchanges, nuclear pore complexes (NPCs) regulate the expression of protein-coding genes. Here, we have implemented transcriptomic and molecular methods to specifically address the impact of the NPC on retroelements, which are present in multiple copies in genomes. We report a novel function for the Nup84 complex, a core NPC building block, in specifically restricting the transcription of LTR-retrotransposons in yeast. Nup84 complex-dependent repression impacts both Copia and Gypsy Ty LTR-retrotransposons, all over the S. cerevisiae genome. Mechanistically, the Nup84 complex restricts the transcription of Ty1, the most active yeast retrotransposon, through the tethering of the SUMO-deconjugating enzyme Ulp1 to NPCs. Strikingly, the modest accumulation of Ty1 RNAs caused by Nup84 complex loss-of-function is sufficient to trigger an important increase of Ty1 cDNA levels, resulting in massive Ty1 retrotransposition. Altogether, our studies expand our understanding of the complex interactions between retrotransposons and the NPC, and highlight the importance for the cells to keep retrotransposon under tight transcriptional control.AUTHOR SUMMARYRetroelements, which replicate by reverse transcription of their RNA into a cDNA that is integrated into the host genetic material, play an important role in the plasticity of eukaryotic genomes. The study of yeast retrotransposons has led to the identification of host factors that limit retroelement mobility, including components of the nuclear pore complex (NPC), most of them still awaiting mechanistic characterization. Here, we investigated the contribution of the Nup84 complex, a core NPC scaffold, to retrotransposon biology in budding yeast. Our findings uncover that the Nup84 complex restricts the transcription of phylogenetically-distinct Ty retroelements. By focusing on Ty1 retrotransposons, we provide evidence that repression by the Nup84 complex depends on the maintenance at the NPC of the SUMO-protease Ulp1, an essential enzyme of the SUMO pathway with multiple targets in the transcription machinery. We finally show that this transcriptional control is critical for genome dynamics, since a small increase in the accumulation of Ty1 RNAs leads to massive retrotransposition. Our data reveal that although relatively abundant, Ty transcripts are limiting for retrotransposition, underscoring the importance of a tight control of their expression. They also characterize a new non-canonical function of NPCs, confirming their connection with genome expression and stability.
Endonuclease domain of non-LTR retrotransposons: loss-of-function mutants and modeling of the R2Bm endonuclease