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

Folkmann AW, Collier SE, Zhan X, Aditi , Ohi MD, Wente SR
Cell. 2013 155 (3): 582-93

PMID: 24243016 · PMCID: PMC3855398 · DOI:10.1016/j.cell.2013.09.023

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.

Copyright © 2013 Elsevier Inc. All rights reserved.

MeSH Terms (9)

Active Transport, Cell Nucleus Arthrogryposis HeLa Cells Humans Mutation Nuclear Pore Nucleocytoplasmic Transport Proteins RNA, Messenger Saccharomyces cerevisiae

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