Repression of ferritin light chain translation by human eIF3

eLife

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[1] Biology Department, Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, United States;Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, United States;Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, United States;California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, United States;Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, United States;California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, United States;Department of Chemistry, University of California, Berkeley, Berkeley, United States;Molecular Biophysics & Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, United States;

关键词: translation regulation;    iron homeostasis;    ferritin light chain;    iron response protein;    eIF3;    Human;   

DOI  :  10.7554/eLife.48193

来源: publisher

【 摘 要 】

10.7554/eLife.48193.001A 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.

【 授权许可】

CC BY