Eukaryotic initiation factor EIF-3.G augments mRNA translation efficiency to regulate neuronal activity
- University of California San Diego, United States
Abstract
The translation initiation complex eIF3 imparts specialized functions to regulate protein expression. However, understanding of eIF3 activities in neurons remains limited despite widespread dysregulation of eIF3 subunits in neurological disorders. Here, we report a selective role of the C. elegans RNA-binding subunit EIF-3.G in shaping the neuronal protein landscape. We identify a missense mutation in the conserved Zinc-Finger (ZF) of EIF-3.G that acts in a gain-of-function manner to dampen neuronal hyperexcitation. Using neuron type-specific seCLIP, we systematically mapped EIF-3.G-mRNA interactions and identified EIF-3.G occupancy on GC-rich 5′UTRs of a select set of mRNAs enriched in activity-dependent functions. We demonstrate that the ZF mutation in EIF-3.G alters translation in a 5′UTR dependent manner. Our study reveals an in vivo mechanism for eIF3 in governing neuronal protein levels to control neuronal activity states and offers insights into how eIF3 dysregulation contributes to neuronal disorders.
Data availability
Raw and processed seCLIP datasets from this study have been uploaded to the Gene Expression Omnibus (GEO) under accession number GSE152704.
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seCLIP of C. elegans EIF-3.G in the cholinergic motor neuronsNCBI Gene Expression Omnibus, GSE152704.
Article and author information
Author details
Funding
National Institute of Health (NS R37 035546)
- Yishi Jin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Anne E West, Duke University School of Medicine, United States
Version history
- Received: March 11, 2021
- Preprint posted: March 16, 2021 (view preprint)
- Accepted: July 28, 2021
- Accepted Manuscript published: July 29, 2021 (version 1)
- Version of Record published: August 10, 2021 (version 2)
Copyright
© 2021, Blazie et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Eukaryotic initiation factor EIF-3.G augments mRNA translation efficiency to regulate neuronal activity
eLife 10:e68336.
https://doi.org/10.7554/eLife.68336
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