Evolution of a transcriptional regulator from a transmembrane nucleoporin

Genes Dev. 2016 May 15;30(10):1155-71. doi: 10.1101/gad.280941.116. Epub 2016 May 19.


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.

Keywords: Nup98; Pom121; evolution; hominoid; nuclear pore complex (NPC); transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Cell Membrane / metabolism
  • Cell Nucleus / metabolism
  • Evolution, Molecular*
  • Exons / genetics
  • Gene Expression Regulation*
  • HeLa Cells
  • Humans
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mutant Proteins / chemistry
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism*
  • Nuclear Localization Signals
  • Nuclear Pore Complex Proteins / chemistry
  • Nuclear Pore Complex Proteins / metabolism*
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Domains
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Solubility
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription Initiation Site
  • Transcription, Genetic*


  • 5' Untranslated Regions
  • Membrane Glycoproteins
  • Mutant Proteins
  • NUP107 protein, human
  • NUP160 protein, human
  • Nuclear Localization Signals
  • Nuclear Pore Complex Proteins
  • Nuclear Proteins
  • Nup98 protein, human
  • POM121 protein, human
  • Protein Isoforms
  • Transcription Factors