Initiation of Translation

The first step in translation is initiation, in which the proper start position on the mRNA is identified. Because of the 'comma-less' nature of the genetic code, only the position of the initiation codon determines the reading frame, and faulty initiation might result in complete distortion of the message as a result of a shift in the reading frame. Precise initiation is therefore the key to accurate translation. The genetic code does not include a specific start signal. Instead, the codon AUG has a dual function that is coupled to the existence of two types of methionine-containing tRNAs. One of these Met-tRNA^Mets is specifically used during initiation and is usually referred to as initiator tRNA . The second Met-tRNA^Met, used only during the elongation process to specify incorporation of the amino acid methionine at internal positions in the protein, is correspondingly referred to as elongator . Several proteins, initiation factors (eIF, eukaryotic initiation factors), provide help to the ribosome during the initiation process.

The initiation process can be divided in several distinct steps.
1. First the ribosome dissociates into its two constituent subunits,called the 40S and 60S subunits. The subunits are prevented from spontaneous reassociation by binding of initiation factor eIF-3 to the small ribosomal subunit.
2. Initiation factor eIF-2 is a GTP-binding protein that specifically recognises initiator tRNA () forming a ternary complex, .
3. The ternary complex binds to the 40S ribosomal subunit.
4. The cap-structure at the 5´end of the messenger RNA is recognised by initiation factor eIF-4F. This factor has a subunit that specifically interacts with the cap-structure (see splicing: cap-structure). Binding of the initiation factor guides the activated 40S subunit, containing the initiator tRNA, to the 5´end of the mRNA. This type of initiation is known as cap-dependent initiation and is the most common type of initiation. Initiation can also occur through an alternative cap-independent initiation mechanism.
5. The mRNA-bound subunit travels along the 5’-untranslated end of the mRNA until it reaches the first AUG codon that will serve as the start codon for the translation process. This process, known as scanning, requires energy (ATP) and additional initiation factors.
6. When the activated 40S subunit has reached the start codon, the 60S subunit binds to the 40S subunit. This reaction requires an additional initiation factor, eIF-5, which hydrolyses the eIF-2-bound GTP, thereby releasing the initiation factors from the ribosome. As a result of the initiation process, the initiator becomes positioned in the ribosomal P-site.