Translation (polypeptide synthesis) involves four key steps: initiation, elongation, translocation and termination

• Prior to translation, tRNA molecules are fused to specific amino acids via a reaction involving ATP hydrolysis
  

  • The function of the ATP is to create a high energy bond that is transferred to the tRNA molecule

  • This ‘charging’ of the tRNA creates stored energy that is used by the ribosome to form a peptide bond

Initiation

• The small ribosomal subunit binds to an initiator tRNA molecule that recognises the start codon (AUG)
  

  • The initiator tRNA is structurally distinct from other tRNA molecules and is only used to begin translation

• This complex then attaches to the 5’-end of the mRNA transcript and moves towards the start codon (5’ → 3’)
  

  • In eukaryotes, the 5’-methyl cap helps to mediate this initial association (other initiation factors are also involved)

• At the start codon, the large ribosomal subunit binds to the initiator tRNA, forming a complete ribosomal complex (all other initiation factors are now released)
  

Elongation

• The large ribosomal subunit has three tRNA binding sites – an A site (aminoacyl), a P site (peptidyl) and an E site (exit)
  

• The initiator tRNA is bound to the central P site and a second tRNA molecule pairs with the next codon in the A site
  

• The amino acid in the P site is covalently attached via a peptide bond (condensation reaction) to the amino acid in the A site
  

• The tRNA in the P site is now deacylated (no amino acid), while the tRNA in the A site carries the peptide chain
  

Translocation

• The ribosome moves along the mRNA strand by one codon position (in a 5’ → 3’ direction)
  

• The deacylated tRNA moves into the E site and is released, while the tRNA carrying the peptide chain moves to the P site
  

• Another tRNA molecules attaches to the next codon in the now unoccupied A site and the process of elongation is repeated
  

Termination

• Elongation and translocation continue in a repeating cycle until the ribosome reaches a stop codon
  

• These codons do not recruit a tRNA molecule, but instead recruit a release factor that signals for translation to stop
  

• The polypeptide is released and the ribosome disassembles back into its two independent subunits