Gle1 Regulates RNA Binding of the DEAD-Box Helicase Ded1 in Its Complex Role in Translation Initiation
AuthorAryanpur, Peyman P.
Regan, Chelsea A.
Collins, John M.
Mittelmeier, Telsa M.
Renner, David M.
Vergara, Ashley M.
Brown, Nicolette P.
Bolger, Timothy A.
AffiliationUniv Arizona, Dept Mol & Cellular Biol
MetadataShow full item record
PublisherAMER SOC MICROBIOLOGY
CitationAryanpur PP, Regan CA, Collins JM, Mittelmeier TM, Renner DM, Vergara AM, Brown NP, Bolger TA. 2017. Gle1 regulates RNA binding of the DEAD-box helicase Ded1 in its complex role in translation initiation. Mol Cell Biol 37:e00139-17. https://doi.org/10.1128/MCB .00139-17.
JournalMOLECULAR AND CELLULAR BIOLOGY
Rights© 2017 American Society for Microbiology. All Rights Reserved.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractDEAD-box proteins (DBPs) are required in gene expression to facilitate changes to ribonucleoprotein complexes, but the cellular mechanisms and regulation of DBPs are not fully defined. Gle1 is a multifunctional regulator of DBPs with roles in mRNA export and translation. In translation, Gle1 modulates Ded1, a DBP required for initiation. However, DED1 overexpression causes defects, suggesting that Ded1 can promote or repress translation in different contexts. Here we show that GLE1 expression suppresses the repressive effects of DED1 in vivo and Gle1 counteracts Ded1 in translation assays in vitro. Furthermore, both Ded1 and Gle1 affect the assembly of preinitiation complexes. Through mutation analysis and binding assays, we show that Gle1 inhibits Ded1 by reducing its affinity for RNA. Our results are consistent with a model wherein active Ded1 promotes translation but inactive or excess Ded1 leads to translation repression. Gle1 can inhibit either role of Ded1, positioning it as a gatekeeper to optimize Ded1 activity to the appropriate level for translation. This study suggests a paradigm for finely controlling the activity of DEAD-box proteins to optimize their function in RNA-based processes. It also positions the versatile regulator Gle1 as a potential node for the coordination of different steps of gene expression.
Note6 month embargo; accepted manuscript posted online 7 August 2017
VersionFinal published version
SponsorsAmerican Cancer Society [13-263-01-RMC]