Involvement in surface antigen expression by a moonlighting FG-repeat nucleoporin in trypanosomes

Components of the nuclear periphery coordinate a multitude of activities, including macromolecular transport, cell-cycle progression and chromatin organization. Nuclear pore complexes (NPCs) mediate nucleocytoplasmic transport, mRNA processing and transcriptional regulation, and NPC components can define regions of high transcriptional activity in some organisms at the nuclear periphery and nucleoplasm. Lineage-specific features underpin several core nuclear functions, and in trypanosomatids, which branched very early from other eukaryotes, unique protein components constitute the lamina, kinetochores and parts of the NPCs. Here we describe an FG-repeat nucleoporin, TbNup53b, that has dual localizations within the nucleoplasm and NPC. In addition to association with nucleoporins, TbNup53b interacts with a knowntrans-splicing component, TSR1, and has a role in controlling expression of surface proteins including the nucleolar periphery-located, procyclin genes. Significantly, while several nucleoporins are implicated in intranuclear transcriptional regulation in metazoa, TbNup53b appears orthologous to components of the yeast/human Nup49/Nup58 complex, for which no transcriptional functions are known. These data suggest that FG-Nups are frequently co-opted to transcriptional functions during evolution, and extends the presence of FG-repeat nucleoporin control of gene expression to trypanosomes, suggesting this is a widespread and ancient eukaryotic feature, as well as underscoring once more flexibility within nucleoporin function.