Plant Translation Initiation Complex eIFiso4F Directs Pokeweed Antiviral Protein to Selectively Depurinate Uncapped Tobacco Etch Virus RNA
| Autor: | Shawn Williams, Christopher Kluge, Artem V. Domashevskiy, Shu-Yuan Cheng |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
RNA Caps
0106 biological sciences 0301 basic medicine Potyvirus 01 natural sciences Biochemistry Ribosome 03 medical and health sciences Peptide Initiation Factors Protein biosynthesis RNA Messenger Peptide Chain Initiation Translational Plant Proteins Messenger RNA biology Oligonucleotide Tobacco etch virus RNA biology.organism_classification Virology female genital diseases and pregnancy complications Tracheophyta 030104 developmental biology Purines Ribosome Inactivating Proteins Type 1 RNA Viral Depurination Translation initiation complex Ribosomes 010606 plant biology & botany |
| Zdroj: | Biochemistry. 56:5980-5990 |
| ISSN: | 1520-4995 0006-2960 |
| Popis: | Pokeweed antiviral protein (PAP) is a ribosome inactivating protein (RIP) that depurinates the sarcin/ricin loop (SRL) of rRNA, inhibiting protein synthesis. PAP depurinates viral RNA, and in doing so, lowers the infectivity of many plant viruses. The mechanism by which PAP accesses uncapped viral RNA is not known, impeding scientists from developing effective antiviral agents for the prevention of the diseases caused by uncapped RNA viruses. Kinetic rates of PAP interacting with tobacco etch virus (TEV) RNA, in the presence and absence of eIFiso4F, were examined, addressing how the eIF affects selective PAP targeting and depurination of the uncapped viral RNA. PAP-eIFs copurification assay and fluorescence resonance energy transfer demonstrate that PAP forms a ternary complex with the eIFiso4G and eIFiso4E, directing the depurination of uncapped viral RNA. eIFiso4F selectively targets PAP to depurinate TEV RNA by increasing PAP's specificity constant for uncapped viral RNA 12-fold, when compared to the depurination of an oligonucleotide RNA that mimics the SRL of large rRNA, and cellular capped luciferase mRNA. This explains how PAP is able to lower infectivity of pokeweed viruses, while preserving its own ribosomes and cellular RNA from depurination: PAP utilizes cellular eIFiso4F in a novel strategy to target uncapped viral RNA. It may be possible to modulate and utilize these PAP-eIFs interactions for their public health benefit; by repurposing them to selectively target PAP to depurinate uncapped viral RNA, many plant and animal diseases caused by these viruses could be alleviated. |
| Databáze: | OpenAIRE |
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