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Publication
Functions of Gle1 are governed by two distinct modes of self-association.
Authors Mason AC, Wente SR
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal The Journal of biological chemistry
Year 2020
Date Published 12/1/2020
Volume : Pages 295 : 16813 - 16825
PubMed Reference 32981894
Abstract Gle1 is a conserved, essential regulator of DEAD-box RNA helicases, with
critical roles defined in mRNA export, translation initiation, translation
termination, and stress granule formation. Mechanisms that specify which, where,
and when DDXs are targeted by Gle1 are critical to understand. In addition to
roles for stress-induced phosphorylation and inositol hexakisphosphate binding
in specifying Gle1 function, Gle1 oligomerizes via its N-terminal domain in a
phosphorylation-dependent manner. However, a thorough analysis of the role for
Gle1 self-association is lacking. Here, we find that Gle1 self-association is
driven by two distinct regions: a coiled-coil domain and a novel 10-amino acid
aggregation-prone region, both of which are necessary for proper Gle1
oligomerization. By exogenous expression in HeLa cells, we tested the function
of a series of mutations that impact the oligomerization domains of the Gle1A
and Gle1B isoforms. Gle1 oligomerization is necessary for many, but not all
aspects of Gle1A and Gle1B function, and the requirements for each interaction
domain differ. Whereas the coiled-coil domain and aggregation-prone region
additively contribute to competent mRNA export and stress granule formation,
both self-association domains are independently required for regulation of
translation under cellular stress. In contrast, Gle1 self-association is
dispensable for phosphorylation and nonstressed translation initiation.
Collectively, we reveal self-association functions as an additional mode of Gle1
regulation to ensure proper mRNA export and translation. This work also provides
further insight into the mechanisms underlying human gle1 disease mutants found
in prenatally lethal forms of arthrogryposis.




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