The DEAD-box RNA helicase Ded1 has a role in the translational response to TORC1 inhibition
AuthorAryanpur, Peyman P
Renner, David M
Mittelmeier, Telsa M
Bolger, Timothy A
AffiliationUniv Arizona, Dept Mol & Cellular Biol
MetadataShow full item record
PublisherAMER SOC CELL BIOLOGY
CitationAryanpur, P. P., Renner, D. M., Rodela, E., Mittelmeier, T. M., Byrd, A., & Bolger, T. A. (2019). The DEAD-box RNA helicase Ded1 has a role in the translational response to TORC1 inhibition. Molecular biology of the cell, mbc-E18.
JournalMOLECULAR BIOLOGY OF THE CELL
RightsCopyright © 2019 Aryanpur et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
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.
AbstractDed1 is a DEAD-box RNA helicase with essential roles in translation initiation. It binds to the eukaryotic initiation factor 4F (eIF4F) complex and promotes 48S preinitiation complex assembly and start-site scanning of 5' untranslated regions of mRNAs. Most prior studies of Ded1 cellular function were conducted in steady-state conditions during nutrient-rich growth. In this work, however, we examine its role in the translational response during target of rapamycin (TOR)C1 inhibition and identify a novel function of Ded1 as a translation repressor. We show that C-terminal mutants of DED1 are defective in down-regulating translation following TORC1 inhibition using rapamycin. Furthermore, following TORC1 inhibition, eIF4G1 normally dissociates from translation complexes and is degraded, and this process is attenuated in mutant cells. Mapping of the functional requirements for Ded1 in this translational response indicates that Ded1 enzymatic activity and interaction with eIF4G1 are required, while homo-oligomerization may be dispensable. Our results are consistent with a model wherein Ded1 stalls translation and specifically removes eIF4G1 from translation preinitiation complexes, thus removing eIF4G1 from the translating mRNA pool and leading to the codegradation of both proteins. Shared features among DED1 orthologues suggest that this role is conserved and may be implicated in pathologies such as oncogenesis.
VersionFinal published version
SponsorsAmerican Cancer Society [RSG-13-263-01-RMC]; Arizona Biomedical Research Commission [ADHS14-082993]
- Yeast Ded1 promotes 48S translation pre-initiation complex assembly in an mRNA-specific and eIF4F-dependent manner.
- Authors: Gupta N, Lorsch JR, Hinnebusch AG
- Issue date: 2018 Oct 3
- Genome-wide analysis of translational efficiency reveals distinct but overlapping functions of yeast DEAD-box RNA helicases Ded1 and eIF4A.
- Authors: Sen ND, Zhou F, Ingolia NT, Hinnebusch AG
- Issue date: 2015 Aug
- Functional interplay between DEAD-box RNA helicases Ded1 and Dbp1 in preinitiation complex attachment and scanning on structured mRNAs in vivo.
- Authors: Sen ND, Gupta N, K Archer S, Preiss T, Lorsch JR, Hinnebusch AG
- Issue date: 2019 Sep 19
- eIF4B stimulates translation of long mRNAs with structured 5' UTRs and low closed-loop potential but weak dependence on eIF4G.
- Authors: Sen ND, Zhou F, Harris MS, Ingolia NT, Hinnebusch AG
- Issue date: 2016 Sep 20
- The DEAD-box protein Ded1 modulates translation by the formation and resolution of an eIF4F-mRNA complex.
- Authors: Hilliker A, Gao Z, Jankowsky E, Parker R
- Issue date: 2011 Sep 16