Repression of ferritin light chain translation by human eIF3
- University of California, Berkeley, United States
- Brandeis University, United States
Abstract
A central problem in human biology remains the discovery of causal molecular links between mutations identified in genome-wide association studies (GWAS) and their corresponding disease traits. This challenge is magnified for variants residing in non-coding regions of the genome. Single-nucleotide polymorphisms (SNPs) in the 5ʹ untranslated region (5ʹ-UTR) of the ferritin light chain (FTL) gene that cause hyperferritinemia are reported to disrupt translation repression by altering iron regulatory protein (IRP) interactions with the FTL mRNA 5ʹ-UTR. Here, we show that human eukaryotic translation initiation factor 3 (eIF3) acts as a distinct repressor of FTL mRNA translation, and eIF3-mediated FTL repression is disrupted by a subset of SNPs in FTL that cause hyperferritinemia. These results identify a direct role for eIF3-mediated translational control in a specific human disease.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
David Trombley McSwiggen
Nicholas T Ingolia
Funding
National Institute of General Medical Sciences (P50 GM102706)
- Mia C Pulos-Holmes
- Daniel N Srole
- Maria G Juarez
- Amy S-Y Lee
- David Trombley McSwiggen
- Nicholas T Ingolia
- Jamie H Cate
National Institute of General Medical Sciences (R01 GM065050)
- Mia C Pulos-Holmes
- Daniel N Srole
- Maria G Juarez
- Jamie H Cate
American Heart Association (16PRE30140013)
- Mia C Pulos-Holmes
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Pulos-Holmes 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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Repression of ferritin light chain translation by human eIF3
eLife 8:e48193.
https://doi.org/10.7554/eLife.48193
