Here we show eIF4A2 is a major effector of the represive miRNA pathway functioning via the Ccr4_Not complex; through its interaction with the Ccr4-Not complex eIF4A2 represses mRNAs at translation initiation. We show evidence that native eIF4A2 has similar properties to chemically inhibited eIF4A1. eIF4A2 exerts its repressive effect by binding purine-rich motifs which are enriched in the 5'UTR directly upstream of the AUG codon.