M03.05.03 Translation and Protein Synthesis

Translation is the process by which the genetic code carried by mRNA is decoded to produce a specific sequence of amino acids, leading to the synthesis of proteins. This process occurs in the cytoplasm and involves ribosomes, tRNA, and various other factors.

Overview of Translation

Translation consists of three main stages:

1. Initiation
2. Elongation
3. Termination

1. Initiation

Initiation is the assembly of the components needed for protein synthesis.

Steps:

• mRNA Binding: The small ribosomal subunit binds to the mRNA at the 5’ cap (in eukaryotes) or the Shine-Dalgarno sequence (in prokaryotes).
• Initiator tRNA: The initiator tRNA, carrying methionine (in eukaryotes) or formyl-methionine (in prokaryotes), binds to the start codon (AUG) on the mRNA.
• Ribosome Assembly: The large ribosomal subunit joins the complex, forming the complete ribosome with the initiator tRNA positioned in the P site.

Side Note: Key Points to Memorize:

• The start codon is always AUG.
• Initiator tRNA carries methionine in eukaryotes and formyl-methionine in prokaryotes.
• The 5’ cap and Shine-Dalgarno sequence facilitate ribosome binding.

2. Elongation

Elongation involves the sequential addition of amino acids to the growing polypeptide chain.

Steps:

1. Codon Recognition: The next tRNA, carrying an amino acid, binds to the A site according to the codon on the mRNA.
2. Peptide Bond Formation: The amino acid in the P site forms a peptide bond with the amino acid in the A site, catalyzed by peptidyl transferase.
3. Translocation: The ribosome moves along the mRNA, shifting the tRNA from the A site to the P site, and the empty tRNA moves to the E site before exiting the ribosome.

Side Note: Key Points to Memorize:

• Elongation occurs in a 5’ to 3’ direction along the mRNA.
• Peptidyl transferase is a ribozyme, not a protein enzyme.
• GTP is hydrolyzed during translocation.

3. Termination

Termination occurs when a stop codon is reached on the mRNA.

Steps:

• Stop Codon Recognition: Release factors (RF) recognize stop codons (UAA, UAG, UGA).
• Release of Polypeptide: The polypeptide chain is released from the tRNA in the P site.
• Disassembly: The ribosomal subunits, mRNA, and release factors disassemble, completing the process.

Side Note: Key Points to Memorize:

• Stop codons do not code for amino acids.
• Release factors are necessary for termination.
• GTP hydrolysis is involved in disassembly.

Regulation and Clinical Relevance

• Regulation: Translation can be regulated at the initiation stage through various mechanisms, including phosphorylation of initiation factors and RNA-binding proteins.
• Antibiotics and Toxins: Several antibiotics (e.g., tetracycline, erythromycin) target bacterial ribosomes, inhibiting protein synthesis. Toxins like diphtheria toxin inhibit eukaryotic elongation factor-2 (eEF-2), blocking translation.

Side Note: Key Points to Memorize:

• Antibiotics can distinguish between prokaryotic and eukaryotic ribosomes.
• Regulation of translation is a critical control point in gene expression.

Table: Key Components in Translation

By understanding the detailed processes of translation and protein synthesis, medical students can appreciate the precision and regulation of gene expression, which is fundamental for cellular function and medical applications.