Initiation of Translation

On the mRNA, the start site for translation is crucial. If translation were to begin one nucleotide before or after the start codon, every codon that follows in the mRNA will be misread, synthesizing a non-functional sequence of amino acids.

Translation begins with the codon AUG, and an initiator tRNA that carries the amino acid Methionine or, the chemically modified formylmethionine in bacteria. 

The initiator tRNA also contains conserved nucleotides that are recognized by proteins called eukaryotic initiation factors, or eIFs. 

Together with eIF2 and GTP, the initiator tRNA binds the P site of the small ribosomal subunit forming the eukaryotic pre-initiation complex.

This complex recognizes the mRNA by interacting with initiation factors eIF4E bound to the 5’ cap, and eIF4G bound to the poly(A) tail-binding proteins.

Powered by ATP hydrolysis, the complex then moves from 5ʹ to 3ʹ direction, with the tRNA anticodon searching for the first AUG sequence on the mRNA.

Upon codon-anticodon recognition, GTP is hydrolyzed and the initiation factors dissociate, allowing the large ribosomal subunit to join the complex and form an intact ribosome.

Now, a new tRNA, carrying the second amino acid, can bind to the A-site on the ribosome and protein synthesis can begin.

In bacteria, mRNAs do not have 5’ caps to initiate translation. 

Instead, each bacterial mRNA contains a leader sequence upstream of the first AUG codon, called the Shine-Dalgarno sequence.

This consensus AGGAGGU sequence serves as the ribosomal binding site by base pairing with a complementary sequence on the 16S rRNA of the small ribosomal subunit. 

Now, the 50S ribosomal subunit can bind to the initiation complex, with the complete ribosome ready to begin translation.