title: 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.
authors.affiliation: Laboratory of Molecular and Cellular Biology, Salk Institute for Biological Studies, La Jolla, California 92037, USA;
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Franks
authors.affiliation: Laboratory of Molecular and Cellular Biology, Salk Institute for Biological Studies, La Jolla, California 92037, USA;
authors.forename: Chris
authors.initials: C
authors.lastname: Benner
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California 92037, USA;
authors.forename: Iñigo
authors.initials: I
authors.lastname: Narvaiza
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California 92037, USA;
authors.forename: Maria C N
authors.initials: MC
authors.lastname: Marchetto
authors.affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA;
authors.forename: Janet M
authors.initials: JM
authors.lastname: Young
authors.affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA; Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA;
authors.forename: Harmit S
authors.initials: HS
authors.lastname: Malik
authors.affiliation: Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California 92037, USA; Center for Academic Research and Training in Anthropogeny (CARTA), La Jolla, California 92093, USA.
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
authors.affiliation: Laboratory of Molecular and Cellular Biology, Salk Institute for Biological Studies, La Jolla, California 92037, USA;
authors.forename: Martin W
authors.initials: MW
authors.lastname: Hetzer
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019913:Nuclear Localization Signals; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D000072417:Protein Domains; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D020121:5' Untranslated Regions; D008562:Membrane Glycoproteins; D050505:Mutant Proteins; C512772:NUP107 protein, human; C440251:NUP160 protein, human; D019913:Nuclear Localization Signals; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; C465451:Nup98 protein, human; C094157:POM121 protein, human; D020033:Protein Isoforms; D014157:Transcription Factors
keywords: Nup98; Pom121; evolution; hominoid; nuclear pore complex (NPC); transcription