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Cell Rep. 2016 Aug 16;16(7):1891-902. doi: 10.1016/j.celrep.2016.07.006. Epub 2016 Jul 28.

A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism.

Author information

1
Tumor Initiation and Maintenance Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
2
School of Pharmaceutical Sciences and Center for Stress Signaling Networks, Xiamen University, Xiang'An South Road, Xiamen 361102, China.
3
G0 Cell Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Okinawa 904-0495, Japan.
4
Universitat Pompeu Fabra, Calle Doctor Aiguader 88, 08003 Barcelona, Spain.
5
Proteomics Facility, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
6
Applied Bioinformatics Core, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
7
Tumor Initiation and Maintenance Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; School of Pharmaceutical Sciences and Center for Stress Signaling Networks, Xiamen University, Xiang'An South Road, Xiamen 361102, China; San Diego Center for Systems Biology, La Jolla, CA 92093, USA. Electronic address: dwolf@sbpdiscovery.org.

Abstract

The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer.

PMID:
27477275
PMCID:
PMC4988921
DOI:
10.1016/j.celrep.2016.07.006
[Indexed for MEDLINE]
Free PMC Article

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