Evolution of a transcriptional regulator from a transmembrane nucleoporin

Abstract

Nuclear pore complexes (NPCs) emerged as nuclear transport channels in eukaryotic cells ∼1.5 billion years ago. While the primary role of NPCs is to regulate nucleo-cytoplasmic transport, recent research suggests that certain NPC proteins have additionally acquired the role of affecting gene expression at the nuclear periphery and in the nucleoplasm in metazoans. Here we identify a widely expressed variant of the transmembrane nucleoporin (Nup) Pom121 (named sPom121, for "soluble Pom121") that arose by genomic rearrangement before the divergence of hominoids. sPom121 lacks the nuclear membrane-anchoring domain and thus does not localize to the NPC. Instead, sPom121 colocalizes and interacts with nucleoplasmic Nup98, a previously identified transcriptional regulator, at gene promoters to control transcription of its target genes in human cells. Interestingly, sPom121 transcripts appear independently in several mammalian species, suggesting convergent innovation of Nup-mediated transcription regulation during mammalian evolution. Our findings implicate alternate transcription initiation as a mechanism to increase the functional diversity of NPC components.

Human Nup98 regulates the localization and activity of DExH/D-box helicase DHX9

“…Data analysis was performed as described in the corresponding dataset and its publication (Franks et al, 2016). …”

Nuclear pore complexes and regulation of gene expression

“…However, in mammalian cells, the transcriptional memory function of Nup98 is independent of NPCs. Interestingly, a soluble variant of the transmembrane nucleoporin Pom121 (sPom121) that arises from alternate transcription initiation was recently discovered to interact with nucleoplasmic Nup98 at the promoters of many target genes to co-regulate their activity [56] (Figure 2), though its role in the regulation of developmental or INF-γ genes has not yet been studied. Like Nup98, Nup153 has also been shown to bind several developmental genes in embryonic stem cells.…”

Cell Biology of theCaenorhabditis elegansNucleus

“…This type of peripheral localization requires cis-acting DNA elements, proteins involved in transcriptional activation and subunits of the NPC. In Drosophila and human cells, NPC subunits also interact with transcriptionally active genes, but, at least in some cases, this interaction occurs away from the nuclear periphery, suggesting that NPC subunits may be "moonlighting" in transcriptional activation (Capelson et al 2010;Kalverda et al 2010;Franks et al 2016). In mammalian cells, developmentally regulated genes shift from a peripheral localization where they are inactive to a nuclear interior localization upon differentiation (for example, see Yao et al 2011).…”