Proposed mechanism of eIF4G2's role in conventional cap-dependent translation. The interference of scanning complexes with 80S ribosomes on an uORF leads to the need for eIF4G2. (A) The small ribosome subunit is attached to the 5′ end of mRNA via interaction between m7G-cap and eIF4F. The 80S ribosome is depicted translating the uORF. (B) eIF4G1 facilitates scanning from the very 5′ end. (C) A collision between the scanning complex and 80S ribosome within the uORF forces a partial loss of eIF4G1 that is brought back to the m7G-cap via interaction with eIF4E. The role of helicase is then assumed by eIF4G2–eIF4A. (D) eIF4G1 is involved in scanning from the very 5′ end, and eIF4G2 participates in scanning after the eIF4G1 loss and thus mediates leaky scanning.
