The cap-binding translation initiation factor, eIF4E, binds a pseudoknot in a viral cap-independent translation element

Biblio

Publication Type:

Journal Article

Source:

Structure, Volume 19, Number 6, p.868-80 (2011)

ISBN:

1878-4186 (Electronic)<br/>0969-2126 (Linking)

Accession Number:

21645857

Keywords:

3' Untranslated Regions, Base Sequence, Binding Sites, Cell-Free System, Computer Simulation, Eukaryotic Initiation Factor-4E/ chemistry, Genes, Reporter, Luciferases, Firefly/genetics/metabolism, Magnesium/chemistry, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Plant Proteins/ chemistry, Protein Binding, Protein Biosynthesis, Recombinant Proteins/ chemistry, RNA Viruses/genetics, RNA, Messenger/ chemistry, Triticum

Abstract:

Eukaryotic initiation factor eIF4E performs a key early step in translation by specifically recognizing the m(7)GpppN cap structure at the 5' end of cellular mRNAs. Many viral mRNAs lack a 5' cap and thus bypass eIF4E. In contrast, we reported a cap-independent translation element (PTE) in Pea enation mosaic virus RNA2 that binds and requires eIF4E for translation initiation. To understand how this uncapped RNA is bound tightly by eIF4E, we employ SHAPE probing, phylogenetic comparisons with new PTEs discovered in panico- and carmoviruses, footprinting of the eIF4E binding site, and 3D RNA modeling using NAST, MC-Fold, and MC-Sym to predict a compact, 3D structure of the RNA. We propose that the cap-binding pocket of eIF4E clamps around a pseudoknot, placing a highly SHAPE-reactive guanosine in the pocket in place of the normal m(7)GpppN cap. This reveals a new mechanism of mRNA recognition by eIF4E.

Notes:

Wang, Zhaohui<br/>Parisien, Marc<br/>Scheets, Kay<br/>Miller, W Allen<br/>R01 GM067104/GM/NIGMS NIH HHS/United States<br/>R01 GM067104-07/GM/NIGMS NIH HHS/United States<br/>Research Support, American Recovery and Reinvestment Act<br/>Research Support, N.I.H., Extramural<br/>Research Support, Non-U.S. Gov't<br/>United States<br/>Structure. 2011 Jun 8;19(6):868-80. doi: 10.1016/j.str.2011.03.013.