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Updated: Jun 1, 2026
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Analysis of Cap-binding Proteins in Human Cells Exposed to Physiological Oxygen Conditions
Published on: December 28, 2016
The cap-binding translation initiation factor, eIF4E, binds a pseudoknot in a viral cap-independent translation
Zhaohui Wang1, Marc Parisien, Kay Scheets
1Plant Pathology Department, and Biochemistry, Biophysics, and Molecular Biology Department, Iowa State University, Ames, IA 50011, USA.
Structure (London, England : 1993)
|June 8, 2011
Summary
This study reveals how a viral RNA lacking a cap structure binds to eukaryotic initiation factor 4E (eIF4E). A novel RNA pseudoknot structure is proposed to mimic the cap, enabling cap-independent translation.
Area of Science:
- Molecular Biology
- Virology
- Structural Biology
Background:
- Eukaryotic translation initiation factor 4E (eIF4E) typically binds the 5' m⁷GpppN cap of cellular mRNAs.
- Many viruses have evolved strategies to initiate translation without a 5' cap.
- A cap-independent translation element (PTE) in Pea enation mosaic virus RNA2 requires eIF4E.
Purpose of the Study:
- To elucidate the mechanism by which uncapped viral RNA binds to eIF4E.
- To determine the structural basis for cap-independent translation initiation mediated by PTE.
Main Methods:
- Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) probing.
- Phylogenetic analysis of newly discovered PTEs in other viruses.
- eIF4E binding site footprinting.
- 3D RNA structure modeling using NAST, MC-Fold, and MC-Sym.
Main Results:
- A compact, 3D structure of the PTE RNA was predicted.
- A pseudoknot structure within the PTE is proposed to be recognized by eIF4E.
- A highly SHAPE-reactive guanosine within the pseudoknot may substitute for the m⁷GpppN cap.
Conclusions:
- eIF4E can recognize uncapped viral RNA through a novel mechanism involving a pseudoknot.
- This pseudoknot structure likely positions key nucleotides within the eIF4E cap-binding pocket.
- This finding provides new insights into alternative mRNA recognition strategies by eIF4E.
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