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5′-UTR recruitment of the translation initiation factor eIF4GI or DAP5 drives cap-independent translation of a subset of human mRNAs

Haizel, Solomon A. ; Bhardwaj, Usha ; Gonzalez, Ruben L. ; Mitra, Somdeb ; Goss, Dixie J.

The Journal of biological chemistry, 2020-08, Vol.295 (33), p.11693-11706 [Peer Reviewed Journal]

United States: Elsevier Inc

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Title:
5′-UTR recruitment of the translation initiation factor eIF4GI or DAP5 drives cap-independent translation of a subset of human mRNAs
Author: Haizel, Solomon A. ; Bhardwaj, Usha ; Gonzalez, Ruben L. ; Mitra, Somdeb ; Goss, Dixie J.
Subjects: 5' Untranslated Regions ; 5′ cap-independent translation enhancer (CITE) ; cap-independent translation ; cell stress ; death-associated protein 5 (DAP5) ; Eukaryotic Initiation Factor-4G - chemistry ; Eukaryotic Initiation Factor-4G - metabolism ; eukaryotic translation initiation factor 4 GI (eIF4GI) ; eukaryotic translation initiation factor 4G (eIF4G) ; fluorescence anisotropy ; gene expression ; Gene Regulation ; Humans ; hypoxia-inducible factor (HIF) ; hypoxia-inducible factor 1α (HIF-1α) ; internal ribosome entry site (IRES) ; mRNA ; Protein Binding ; Protein Biosynthesis ; Protein Domains ; protein synthesis ; protein-nucleic acid interaction ; RNA Caps - metabolism ; RNA, Messenger - metabolism
Is Part Of: The Journal of biological chemistry, 2020-08, Vol.295 (33), p.11693-11706
Notes: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Edited by Ronald C. Wek
Description: During unfavorable conditions (e.g. tumor hypoxia or viral infection), canonical, cap-dependent mRNA translation is suppressed in human cells. Nonetheless, a subset of physiologically important mRNAs (e.g. hypoxia-inducible factor 1α [HIF-1α], fibroblast growth factor 9 [FGF-9], and p53) is still translated by an unknown, cap-independent mechanism. Additionally, expression levels of eukaryotic translation initiation factor 4GI (eIF4GI) and of its homolog, death-associated protein 5 (DAP5), are elevated. By examining the 5′ UTRs of HIF-1α, FGF-9, and p53 mRNAs and using fluorescence anisotropy binding studies, luciferase reporter-based in vitro translation assays, and mutational analyses, we demonstrate here that eIF4GI and DAP5 specifically bind to the 5′ UTRs of these cap-independently translated mRNAs. Surprisingly, we found that the eIF4E-binding domain of eIF4GI increases not only the binding affinity but also the selectivity among these mRNAs. We further demonstrate that the affinities of eIF4GI and DAP5 binding to these 5′ UTRs correlate with the efficiency with which these factors drive cap-independent translation of these mRNAs. Integrating the results of our binding and translation assays, we conclude that eIF4GI or DAP5 is critical for recruitment of a specific subset of mRNAs to the ribosome, providing mechanistic insight into their cap-independent translation.
Publisher: United States: Elsevier Inc
Language: English

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5′-UTR recruitment of the translation initiation factor eIF4GI or DAP5 drives cap-independent translation of a subset of human mRNAs

Haizel, Solomon A. ; Bhardwaj, Usha ; Gonzalez, Ruben L. ; Mitra, Somdeb ; Goss, Dixie J.

United States: Elsevier Inc

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