Nup42 and IP coordinate Gle1 stimulation of Dbp5/DDX19B for mRNA export in yeast and human cells.

Adams RL, Mason AC, Glass L, Aditi , Wente SR
Traffic. 2017 18 (12): 776-790

PMID: 28869701 · PMCID: PMC5677552 · DOI:10.1111/tra.12526

The mRNA lifecycle is driven through spatiotemporal changes in the protein composition of mRNA particles (mRNPs) that are triggered by RNA-dependent DEAD-box protein (Dbp) ATPases. As mRNPs exit the nuclear pore complex (NPC) in Saccharomyces cerevisiae, this remodeling occurs through activation of Dbp5 by inositol hexakisphosphate (IP )-bound Gle1. At the NPC, Gle1 also binds Nup42, but Nup42's molecular function is unclear. Here we employ the power of structure-function analysis in S. cerevisiae and human (h) cells, and find that the high-affinity Nup42-Gle1 interaction is integral to Dbp5 (hDDX19B) activation and efficient mRNA export. The Nup42 carboxy-terminal domain (CTD) binds Gle1/hGle1B at an interface distinct from the Gle1-Dbp5/hDDX19B interaction site. A nup42-CTD/gle1-CTD/Dbp5 trimeric complex forms in the presence of IP . Deletion of NUP42 abrogates Gle1-Dbp5 interaction, and disruption of the Nup42 or IP binding interfaces on Gle1/hGle1B leads to defective mRNA export in S. cerevisiae and human cells. In vitro, Nup42-CTD and IP stimulate Gle1/hGle1B activation of Dbp5 and DDX19B recombinant proteins in similar, nonadditive manners, demonstrating complete functional conservation between humans and S. cerevisiae. Together, a highly conserved mechanism governs spatial coordination of mRNP remodeling during export. This has implications for understanding human disease mutations that perturb the Nup42-hGle1B interaction.

© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

MeSH Terms (10)

Active Transport, Cell Nucleus DEAD-box RNA Helicases Humans Nuclear Pore Nuclear Pore Complex Proteins Nucleocytoplasmic Transport Proteins Phytic Acid RNA, Messenger Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins

Connections (1)

This publication is referenced by other Labnodes entities:

Links