Date of Degree

2-2022

Document Type

Dissertation

Degree Name

Ph.D.

Program

Chemistry

Advisor

Dixie J Goss

Committee Members

Ruben Gonzalez

Frida Kleiman

David Jeruzalmi

Subject Categories

Biochemistry, Biophysics, and Structural Biology

Keywords

Viral Translation, RNA virus, Translation initiation, Fluorescence Anisotropy

Abstract

Barley Yellow Dwarf Virus (BYDV) is a positive strand RNA plant virus that translates without using a 5′ 7-methylguanosine cap or a 3′ poly-adenosine tail, features that are required for canonical mRNA translation. BYDV’s non-canonical translation relies on RNA structures in the 5′ and 3′ untranslated regions (UTRs) to recruit eukaryotic initiation factors (eIFs) and ribosomes. BYDV’s 3′ translation enhancer (BTE) is a cruciform structure capable of recruiting the cap-binding complex eIF4F, the large scaffolding complex eIF3, and the 40S ribosomal subunit. Together eIF3, eIF4F, and BTE influence factor binding and 40S recruitment on the 5′ UTR and play a key role in facilitating BYDV translation. This report focuses on eIF3 by providing and analyzing data that suggest novel eIF3 functionality and that expand upon the previous model of BYDV translation initiation to include eIF3 interactions with the UTRs and other factors. Specifically, we show that eIF3 can act as a dynamic, eIF4F-responsive bridge between specific loops found in both of BYDV’s UTRs. This report also provides insight into some of the broader applications of these discoveries by highlighting both parallels and distinctions between eIF-RNA interactions of BYDV and similar interactions found in other, non-canonically translating viral mRNAs and cellular mRNAs.

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