**10. Inhibition of translation initiation**

There was an observation by a group, where it was observed that the central domain of Argonaute proteins has sequence similarities to the cytoplasmic cap-binding protein *eIF4E* [eukaryotic translation initiation factor 4E], which is necessary for the cap-dependent transla‐ tion initiation in the cell. *eIF4E* binds to the m7Gppp-cap structure of mRNAs by stacking the methylated base of the cap between two tryptophans. At the equivalent position of the tryptophans in eIF4E, Argonaute proteins have phenylalanines that could mediate a similar interaction between the molecules. Consistently, Kiriakidou et al. [26] showed that human Argonaute 2 (AGO2) binds to m7GTP present on Sepharose beads. It was shown that substi‐ tuting one or both AGO2 phenylalanines with valine residues suspended the silencing activity. Using human cells it was shown that AGO2 associates with both *eIF6* and large ribosomal subunits. By binding to the large ribosomal subunit, *eIF6* prevents this subunit from joining with the small ribosomal subunit prematurely. *AGO2* recruits *eIF6*, thus stopping the associ‐ ation of the large and small ribosomal subunits, causing translation repression [8, 27].
