Eukaryotic initiation factor 3 (eIF3), an essential multi-protein complex involved in translation initiation, is composed of 12 tightly associated subunits in humans. While the overall structure of eIF3 is known, the mechanism of its assembly and structural consequences of dysregulation of eIF3 subunit expression seen in many cancers is largely unknown. Here we show that subunits in eIF3 assemble into eIF3 in an interdependent manner. Assembly of eIF3 is governed primarily by formation of a helical bundle, composed of helices extending C-terminally from PCI-MPN domains in eight subunits. We propose that, while the minimal subcomplex of human-like eIF3 functional for translation initiation in cells consists of subunits a, b, c, f, g, i, and m, numerous other eIF3 subcomplexes exist under circumstances of subunit over- or underexpression. Thus, eIF3 subcomplexes formed or "released" due to dysregulated subunit expression may be determining factors contributing to eIF3-related cancers.
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| http://dx.doi.org/10.1016/j.str.2016.02.024 | DOI Listing |
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- Translation initiation significantly influences gene expression in eukaryotes, with eukaryotic initiation factor 3 (eIF3) playing a key role in recruiting ribosomes.
- This study examined how eIF3's binding to specific 5'-untranslated regions (5'-UTRs) of mRNAs leads to varying protein outputs, finding that it binds to a specific motif, AMAYAA, in some 5'-UTRs.
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