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.
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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
