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bioRxiv · 10.1101/316299

Orthogonal regulation of ferritin translation by human eIF3 and the iron response proteins

Pulos, M. C.·Srole, D. N.·McSwiggen, D. T.·Ingolia, N. T.·Cate, J.
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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 5 untranslated region (5-UTR) of the ferritin light chain (FTL) gene that cause hyperferritinemia are thought to disrupt translation repression by altering iron regulatory protein (IRP) interactions with the FTL mRNA 5-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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Pulos, M. C., Srole, D. N., McSwiggen, D. T., Ingolia, N. T., Cate, J.. 2018-05-08. Orthogonal regulation of ferritin translation by human eIF3 and the iron response proteins. https://doi.org/10.1101/316299

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