Gene Expression Chapter 2: RNA Translation

Gene Expression 2: RNA Translation and Genetic Code

• Learning Objectives (ILOs): Students will be able to discuss the rules of the genetic code, correlate the functions of different RNAs in translation, describe the process of translation, and interpret the role of translation and post-translational modification in health and disease.

What is Translation?

• Translation is the process of converting the nucleotide sequence of messenger RNA (mRNA, codons) into an amino acid sequence to synthesize proteins.
• Each codon is a triplet code (a sequence of 3 nucleotides).
• The collection of codons forms the genetic code.
• Protein biosynthesis is translation because it converts nucleic acid's 4-letter language/structure into proteins' 20-letter language/structure.

Requirements of Translation

• mRNA carries genetic information.
• tRNA is an adapter molecule; one end recognizes an amino acid, the other end recognizes a complementary codon on mRNA. At least one tRNA exists for each amino acid.
• Ribosomes coordinate the interactions between mRNA, tRNA, enzymes, and protein factors for protein synthesis.

Genetic Code

• The genetic code describes the relationship between the nucleotide sequence in DNA or mRNA and the amino acids in a polypeptide chain.
• Multiple codons can specify the same amino acid (degenerate).
• The third codon position is less crucial than the first two (wobble theory).
• The genetic code is unambiguous (each codon specifies only one amino acid), non-overlapping (the code reads from a fixed starting point without punctuation), and universal (the same code words used across organisms).
• There is one start codon (AUG, methionine).
• There are three stop codons (UAA, UAG, UGA).
• The genetic information on mRNA is read 5' to 3'.

Protein Biosynthesis Stages:

• Initiation: The 80S eukaryotic ribosome dissociates into 40S and 60S subunits.
  • Initiation factors (eIFs) prevent subunit re-association.
  • GTP, ATP, tRNA/mRNA, and amino acids are involved.
  • mRNA binds to the small ribsomal subunit.
  • Methionine-tRNA binds (initiation complex forms)
  • Large ribosomal subunit binds to the complex.
• Elongation: A cyclic process with three key steps:
  • Aminoacyl-tRNA binding to the A site on the ribosome.
  • Peptide bond formation between amino acids.
  • Translocation of the ribosome to the next codon.
• Termination: A stop codon (UAA, UAG, or UGA) enters the A site. No tRNA recognizes stop codons, so Release Factors recognize them, causing the polypeptide to be released.

Characteristics of the Genetic Code

• Degeneracy: Multiple codons can specify the same amino acid.
• Unambiguity: Each codon specifies only one amino acid.
• Non-overlapping: Codons are read sequentially without gaps.
• Commaless: The code reads continually without punctuation between codons.
• Universality: The same code applies to all organisms.

Protein Maturation Stages

• Protein folding is assisted by molecular chaperones.
• Misfolded proteins are often targeted for destruction.
• Post-translational processing modifies proteins:
  • Proteolysis: Removal of amino acid sequences (signal peptides and others).
  • Modifications of individual amino acids: Hydroxylation, phosphorylation, glycosylation, and acylation.

Clinical Implications

• Antibiotics and toxins can interfere with bacterial or eukaryotic protein synthesis.