Internal initiation of translation mediated by the 5′ leader of a cellular mRNA

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Abstract
A RIBOSOME-SCANNING model has been proposed to explain the initiation of eukaryotic messenger RNAs1 in which binding of the 43S ternary ribosomal subunit near or at the 5′ end of the mRNA is facilitated by an interaction between the methylated cap-structure at the end of the mRNA and the cap-binding protein complex eIF–4F (refs 2, 3). But picornaviral mRNAs do not have a 5′ terminal cap structure and are translated by internal ribosome binding4–7. A cellular mRNA, encoding the immunoglobulin heavy-chain binding protein, can be translated in poliovirus-infected cells at a time when cap-dependent translation of host cell mRNAs is inhibited8. We report here that the 5′ leader of the binding protein mRNA can directly confer internal ribosome binding to an mRNA in mammalian cells, indicating that translation initiation by an internal ribosome-binding mechanism is used by eukaryotic mRNAs.