Structural studies of the eIF4E-VPg complex reveal a direct competition for capped RNA: Implications for translation

RNA processing including covalent modifications (e.g., the addition of the methyl-7-guanosine [m⁷G] "cap" on the 5' end of transcripts) centrally influences the proteome. For example, eIF4E recruits RNAs for translation by binding the m⁷G cap. eIF4E is engaged and controlled by the binding of factors to its dorsal surface while leaving its m⁷G cap-binding site free for RNA recruitment. Here, we unexpectedly found that a small viral protein, viral genome-linked protein (VPg), directly binds the cap-binding site of eIF4E, indicating that eIF4E can additionally be controlled through direct competition with its cap-binding site. Furthermore, VPg-RNA conjugates also bind eIF4E and are templates for translation, suggesting that VPg may substitute for the m⁷G cap during infection.