15.3 Stages of translation: initiation, elongation, and termination

Translation is the process of converting genetic information into proteins. It's a complex dance of molecules, involving ribosomes, mRNA, and tRNAs. The process is divided into initiation, elongation, and termination phases, each with its own set of players and steps.

Prokaryotes and eukaryotes share the basic translation machinery, but differ in the details. Eukaryotes have more complex initiation processes and additional factors involved. Understanding these differences is key to grasping how cells make proteins.

Translation Initiation

Initiation of translation

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• Prokaryotic initiation involves:
  • 30S ribosomal subunit recognizes and binds to the Shine-Dalgarno sequence located upstream of the start codon (AUG) on the mRNA
  • Initiation factors (IF1, IF2, IF3) and the initiator tRNA (fMet-tRNA$^{\text{fMet}}$) associate with the 30S subunit to form the 30S initiation complex
  • 50S ribosomal subunit joins the 30S initiation complex, forming the complete 70S initiation complex ready to start translation
• Eukaryotic initiation is more complex and involves:
  • Formation of the 43S pre-initiation complex
    • 40S ribosomal subunit binds to eukaryotic initiation factors eIF1, eIF1A, eIF3, and eIF5
    • Ternary complex consisting of eIF2 bound to GTP and the initiator tRNA (Met-tRNA$_i^{\text{Met}}$) joins the 40S subunit
  • Recruitment of the mRNA to the 43S pre-initiation complex
    • eIF4F complex (composed of eIF4E, eIF4A, and eIF4G) binds to the 5' cap structure of the mRNA
    • 43S pre-initiation complex is recruited to the mRNA, forming the 48S initiation complex
    • 48S complex scans along the mRNA in the 5' to 3' direction until it locates the start codon (AUG)
  • Joining of the 60S ribosomal subunit to form the 80S initiation complex
    • Upon start codon recognition, eIF5 stimulates GTP hydrolysis by eIF2, leading to the release of initiation factors
    • 60S ribosomal subunit joins the complex, forming the complete 80S initiation complex ready to begin translation elongation

Translation Elongation

Elongation and peptidyl transferase

• The elongation cycle consists of three main steps:
  1. Binding of the aminoacyl-tRNA to the A site of the ribosome
     • Elongation factor EF-Tu (eEF1A in eukaryotes) binds aminoacyl-tRNA and GTP, forming a ternary complex
     • The ternary complex enters the A site of the ribosome, allowing codon-anticodon recognition
     • Correct codon-anticodon pairing triggers GTP hydrolysis by EF-Tu (eEF1A), releasing the aminoacyl-tRNA in the A site
  2. Formation of the peptide bond catalyzed by the peptidyl transferase center
     • The peptidyl transferase reaction occurs in the large ribosomal subunit (50S in prokaryotes, 60S in eukaryotes)
     • The growing polypeptide chain attached to the tRNA in the P site is transferred to the amino acid on the tRNA in the A site, forming a new peptide bond
  3. Translocation of the ribosome along the mRNA
     • Elongation factor EF-G (eEF2 in eukaryotes) binds to the ribosome and hydrolyzes GTP, providing energy for translocation
     • The ribosome shifts by one codon, moving the tRNA-peptide complex from the A site to the P site and the deacylated tRNA from the P site to the E site
     • The deacylated tRNA dissociates from the E site, and the elongation cycle repeats, adding one amino acid at a time to the growing polypeptide chain

Translation Termination

Termination and polypeptide release

• Recognition of the stop codon by release factors
  • When one of the three stop codons (UAA, UAG, or UGA) enters the A site of the ribosome, it signals the end of the coding sequence
  • Release factors (RF1 and RF2 in prokaryotes, eRF1 in eukaryotes) recognize and bind to the stop codon in the A site
• Release of the completed polypeptide chain
  • Binding of the release factors triggers the hydrolysis of the ester bond between the polypeptide chain and the tRNA in the P site
  • The completed polypeptide chain is released from the ribosome, and translation is terminated
• Recycling of the ribosomal subunits
  • In prokaryotes, the ribosome recycling factor (RRF) and EF-G work together to promote the dissociation of the ribosomal subunits
  • The mRNA and deacylated tRNA are released, and the ribosomal subunits are recycled for another round of translation
  • In eukaryotes, the recycling process is less well understood, but it is known that eEF2 is involved in the dissociation of the ribosomal subunits

Prokaryotic vs eukaryotic translation

• Similarities between prokaryotic and eukaryotic translation
  • The fundamental steps of initiation, elongation, and termination are conserved across all domains of life
  • The genetic code is nearly universal, with a few minor exceptions (mitochondrial code)
  • Ribosomes are composed of a small and a large subunit that work together to synthesize proteins
• Key differences between prokaryotic and eukaryotic translation
  • Initiation
    • Prokaryotes use the Shine-Dalgarno sequence to recruit the ribosome, while eukaryotes use the 5' cap and scanning mechanism
    • Prokaryotic ribosomes have 30S and 50S subunits, while eukaryotic ribosomes have 40S and 60S subunits
    • Eukaryotes have a larger number of initiation factors and a more complex initiation process compared to prokaryotes
  • Elongation
    • Prokaryotes use elongation factors EF-Tu and EF-G, while eukaryotes use eEF1A and eEF2
  • Termination
    • Prokaryotes employ release factors RF1 and RF2, while eukaryotes use eRF1 for stop codon recognition and peptide release
  • Ribosome recycling
    • Prokaryotes require the ribosome recycling factor (RRF) for subunit dissociation, while eukaryotes do not have a direct homolog of RRF
  • mRNA structure and processing
    • Prokaryotic mRNA is polycistronic (multiple coding sequences on a single mRNA), while eukaryotic mRNA is monocistronic (one coding sequence per mRNA)
    • Eukaryotic mRNA undergoes post-transcriptional modifications, such as 5' capping and 3' polyadenylation, which are absent in prokaryotic mRNA