Translation initiation in eukaryotic cells

Three different mechanisms are reviewed by which protein translation can be initiated. The scanning mechanism, in which the ribosome attaches to the 5 'cap structure before migrating along the mRNA in a 5' to 3' direction unti l an AUG start codon is encountered, is the most thoroughly characterized. The function of initiation factors in the formation of the ribosomal comple x and its attachment to the mRNA are considered. Furthermore distinct mecha nisms such as internal initiation, bg which the ribosome is directly recrui ted at a site downstream of the 5' cap (IRES), and ribosomal shunting which allows a 5'cap-bound ribosome to bypass stable secondary structures in the untranslated 5' region intervening between the cap and the AUG start codon are also described, The importance of the novel mechanisms for the constru ction of MLV-IRES vectors in which internal initiation allows co-expression of two distinct gene products from a single mRNA molecule is considered, a s is the possibility that internally initiated translation may represent a novel level at which transgene expression may be controlled.