Eukaryotic initiation factor EIF-3.G augments mRNA translation efficiency to regulate neuronal activity

  1. Stephen M Blazie
  2. Seika Takayanagi-Kiya
  3. Katherine M McCulloch
  4. Yishi Jin  Is a corresponding author
  1. 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.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Stephen M Blazie

    Section of Neurobiology, Division of Biological Sciences, University of California San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Seika Takayanagi-Kiya

    Section of Neurobiology, Division of Biological Sciences, University of California San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Katherine M McCulloch

    Section of Neurobiology, Division of Biological Sciences, University of California San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yishi Jin

    Section of Neurobiology, Division of Biological Sciences, University of California San Diego, La Jolla, United States
    For correspondence
    yijin@ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9371-9860

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

  1. Anne E West, Duke University School of Medicine, United States

Version history

  1. Received: March 11, 2021
  2. Preprint posted: March 16, 2021 (view preprint)
  3. Accepted: July 28, 2021
  4. Accepted Manuscript published: July 29, 2021 (version 1)
  5. 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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  1. Stephen M Blazie
  2. Seika Takayanagi-Kiya
  3. Katherine M McCulloch
  4. Yishi Jin
(2021)
Eukaryotic initiation factor EIF-3.G augments mRNA translation efficiency to regulate neuronal activity
eLife 10:e68336.
https://doi.org/10.7554/eLife.68336

Share this article

https://doi.org/10.7554/eLife.68336

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