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Repression of ferritin light chain translation by human eIF3.

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 reported 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.

SUBMITTER: Pulos-Holmes MC

PROVIDER: S-EPMC6721798 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Repression of ferritin light chain translation by human eIF3.

Pulos-Holmes Mia C MC Srole Daniel N DN Juarez Maria G MG Lee Amy S-Y AS McSwiggen David T DT Ingolia Nicholas T NT Cate Jamie H JH

eLife 20190815

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 (<i>FTL</i>) gene that cause hyperferritinemia are reported to disrupt translation repression by altering iron re ...[more]

PMID: 31414986

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