Gle1 functions during mRNA export in an oligomeric complex that is altered in human disease

Cell. 2013 Oct 24;155(3):582-93. doi: 10.1016/j.cell.2013.09.023. Epub 2013 Oct 24.


The conserved multifunctional protein Gle1 regulates gene expression at multiple steps: nuclear mRNA export, translation initiation, and translation termination. A GLE1 mutation (FinMajor) is causally linked to human lethal congenital contracture syndrome-1 (LCCS1); however, the resulting perturbations on Gle1 molecular function were unknown. FinMajor results in a proline-phenylalanine-glutamine peptide insertion within the uncharacterized Gle1 coiled-coil domain. Here, we find that Gle1 self-associates both in vitro and in living cells via the coiled-coil domain. Electron microscopy reveals that high-molecular-mass Gle1 oligomers form ?26 nm diameter disk-shaped particles. With the Gle1-FinMajor protein, these particles are malformed. Moreover, functional assays document a specific requirement for proper Gle1 oligomerization during mRNA export, but not for Gle1's roles in translation. These results identify a mechanistic step in Gle1's mRNA export function at nuclear pore complexes and directly implicate altered export in LCCS1 disease pathology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Active Transport, Cell Nucleus
  • Arthrogryposis / genetics
  • Arthrogryposis / metabolism*
  • Arthrogryposis / pathology
  • HeLa Cells
  • Humans
  • Mutation
  • Nuclear Pore / metabolism
  • Nucleocytoplasmic Transport Proteins / metabolism*
  • RNA, Messenger / metabolism*
  • Saccharomyces cerevisiae / metabolism


  • Gle1 protein, human
  • Nucleocytoplasmic Transport Proteins
  • RNA, Messenger

Supplementary concepts

  • Lethal congenital contracture syndrome 1