M03.04.04 Translation (Protein Synthesis)

Translation is the biological process by which proteins are synthesized from amino acids based on the information encoded in messenger RNA (mRNA). This complex process involves the formation of peptide bonds between amino acids, facilitated by ribosomes, tRNA, and various protein factors.

Overview of Translation

Translation occurs in three main stages: initiation, elongation, and termination. During this process, the ribosome reads the mRNA sequence and assembles the corresponding amino acids to form a polypeptide chain.

Key Concepts

• Peptide Bond Formation: A peptide bond is formed between the carboxyl group of one amino acid and the amino group of another, as illustrated in Figure 1.
• tRNA: Transfer RNA (tRNA) molecules transport specific amino acids to the ribosome, where the peptide bonds are formed.

Steps of Translation

1. Initiation

Initiation marks the beginning of translation. The process involves the following steps:

• Ribosomal Binding:
  • In prokaryotes, the 16S rRNA of the small ribosomal subunit binds to the Shine-Dalgarno sequence on the mRNA.
  • In eukaryotes, the small subunit binds to the 5′ cap of the mRNA and scans for the first AUG start codon.
• tRNA Binding:
  • The initiator tRNA binds to the start codon (AUG) through complementary base pairing. In prokaryotes, this tRNA carries formylmethionine (fMet), while in eukaryotes, it carries methionine (Met).
• Formation of the Initiation Complex: The large ribosomal subunit joins the small subunit, completing the initiation complex.

2. Elongation

Elongation involves the addition of amino acids to the growing polypeptide chain through a series of cycles:

• tRNA Binding to the A Site:
  • A charged tRNA enters the A site of the ribosome, corresponding to the codon on the mRNA.
• Peptide Bond Formation:
  • The enzyme peptidyl transferase catalyzes the formation of a peptide bond between the amino acid in the A site and the growing polypeptide chain in the P site.
• Translocation:
  • The ribosome moves along the mRNA, shifting the tRNA and growing the polypeptide chain into the P site, making the A site available for the next charged tRNA.

3. Termination

Termination occurs when a stop codon enters the A site:

• Stop Codon Recognition: The ribosome recognizes one of the three stop codons (UAA, UAG, UGA) in the A site.
• Release Factor Action: Peptidyl transferase, along with a release factor, hydrolyzes the bond between the completed polypeptide and the tRNA in the P site, releasing the newly synthesized protein.
• Recycling Components: The mRNA, ribosome, tRNA, and associated factors can be reused for subsequent rounds of translation.

Summary Table of Translation Stages

Points to Remember

• Initiation begins with the binding of the small ribosomal subunit to mRNA.
• The A site is where new tRNAs enter, while the P site holds the growing peptide chain.
• Peptidyl transferase catalyzes peptide bond formation during elongation.
• Translation involves multiple factors, including initiation factors (IF), elongation factors (EF), and release factors.
• Prokaryotic and eukaryotic translation processes have distinct initiation mechanisms.

Bibliography

• Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Molecular Biology of the Cell (4th ed.). Garland Science.
• Lodish, H., Berk, A., Kaiser, C., Krieger, M., Scott, M. P., & Bretscher, A. (2008). Molecular Cell Biology (6th ed.). W. H. Freeman.
• Nelson, D. L., & Cox, M. M. (2017). Lehninger Principles of Biochemistry (7th ed.). W. H. Freeman.
• Brown, T. A. (2006). Gene Cloning and DNA Analysis: An Introduction (6th ed.). Wiley-Blackwell.