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

Significance RNA processing including covalent modifications (e.g., the addition of the methyl-7-guanosine [m7 G] “cap” on the 5′ end of transcripts) centrally influences the proteome. For example, eIF4E recruits RNAs for translation by binding the m7 G cap. eIF4E is engaged and controlled by the binding of factors to its dorsal surface while leaving its m7 G 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 m7 G cap during infection.