Human EIF3: from 'blobology' to Biological Insight
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Translation in eukaryotes is highly regulated during initiation, a process impacted by numerous readouts of a cell's state. There are many cases in which cellular messenger RNAs likely do not follow the canonical 'scanning' mechanism of translation initiation, but the molecular mechanisms underlying these pathways are still being uncovered. Some RNA viruses such as the hepatitis C virus use highly structured RNA elements termed internal ribosome entry sites (IRESs) that commandeer eukaryotic translation initiation, by using specific interactions with the general eukaryotic translation initiation factor eIF3. Here, I present evidence that, in addition to its general role in translation, eIF3 in humans and likely in all multicellular eukaryotes also acts as a translational activator or repressor by binding RNA structures in the 5'-untranslated regions of specific mRNAs, analogous to the role of the mediator complex in transcription. Furthermore, eIF3 in multicellular eukaryotes also harbours a 5' 7-methylguanosine cap-binding subunit-eIF3d-which replaces the general cap-binding initiation factor eIF4E in the translation of select mRNAs. Based on results from cell biological, biochemical and structural studies of eIF3, it is likely that human translation initiation proceeds through dozens of different molecular pathways, the vast majority of which remain to be explored.This article is part of the themed issue 'Perspectives on the ribosome'.
Cellular translational enhancer elements that recruit eukaryotic initiation factor 3.
Koubek J, Kaur J, Bhandarkar S, Lewis C, Niederer R, Stanciu A RNA. 2024; 31(2):193-207.
PMID: 39626887 PMC: 11789482. DOI: 10.1261/rna.080310.124.
LIN-66 mediates EIF-3/eIF3-dependent protein translation via a cold-shock domain.
Blazie S, Fortunati D, Zhao Y, Jin Y Life Sci Alliance. 2024; 7(9).
PMID: 38886018 PMC: 11184513. DOI: 10.26508/lsa.202402673.
Non-canonical mRNA translation initiation in cell stress and cancer.
Mahe M, Rios-Fuller T, Katsara O, Schneider R NAR Cancer. 2024; 6(2):zcae026.
PMID: 38828390 PMC: 11140632. DOI: 10.1093/narcan/zcae026.
A dynamic compositional equilibrium governs mRNA recognition by eIF3.
Ide N, Gentry R, Rudbach M, Yoo K, Velez P, Comunale V bioRxiv. 2024; .
PMID: 38712078 PMC: 11071631. DOI: 10.1101/2024.04.25.581977.
JUN mRNA translation regulation is mediated by multiple 5' UTR and start codon features.
Gonzalez-Sanchez A, Castellanos-Silva E, Diaz-Figueroa G, Cate J PLoS One. 2024; 19(3):e0299779.
PMID: 38483896 PMC: 10939236. DOI: 10.1371/journal.pone.0299779.