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RNA and the Genetic Code

May 28, 2024

RNA and the Genetic Code

Key Concepts

  • Organisms must store and pass on genetic information to future generations and express it to carry out life processes.
  • Genetic information is encoded in DNA and RNA with nitrogenous bases, while proteins are composed of amino acids.
  • The genetic code translates genetic information into proteins through transcription (DNA to RNA) and translation (RNA to protein).
  • A gene is a unit of DNA encoding a specific protein or RNA molecule.

Central Dogma of Molecular Biology

  1. Transcription: DNA ➡️ RNA
    • Synthesis direction: 5′ to 3′.
    • Complementary and anti-parallel to the DNA template strand.
  2. Translation: RNA ➡️ Protein
    • Ribosomes translate mRNA in the 5′ to 3′ direction.
    • Synthesizes protein from amino (N-terminus) to carboxyl terminus (C-terminus).

Types of RNA

  1. mRNA (Messenger RNA)
    • Carries genetic information from DNA to ribosome for protein synthesis.
    • Synthesized in the nucleus, transported to cytoplasm.
    • Stability allows gene expression regulation.
    • Eukaryotic mRNA is monocistronic; prokaryotic mRNA can be polycistronic.
  2. tRNA (Transfer RNA)
    • Brings correct amino acid to the ribosome during protein synthesis.
    • Contains an anticodon complementary to mRNA's codon.
    • Catalyzes peptide bond formation between amino acids.
  3. rRNA (Ribosomal RNA)
    • Structural and functional component of ribosomes.
    • Involved in catalyzing peptide bonds and positioning mRNA/tRNA.

Codons

  • Basic unit: Three-letter word (codon) translating into an amino acid.
  • Genetic code consists of 64 codons.
    • 61 codons for 20 amino acids.
    • 3 codons signal translation termination.
  • Codons read in 5′ to 3′ direction, unambiguous (one codon per amino acid).
  • Start Codon: AUG (methionine)
  • Stop Codons: UAA, UAG, UGA

Genetic Code Characteristics

  • Degenerate Code: Multiple codons can specify same amino acid.
    • Example: Six codons specify serine.
  • Wobble Position: Third base in codon can vary without altering amino acid (silent mutation).

Mutations

  1. Point Mutations
    • Silent Mutation: No effect on protein (e.g., GTA to GTT, still valine).
    • Missense Mutation: Substitutes one amino acid for another (e.g., CCC to ACC).
    • Nonsense Mutation: Codon becomes a premature stop codon (e.g., TAC to TAG).
  2. Frame Shift Mutations
    • Addition or deletion of nucleotides shifts reading frame.
    • Results in altered amino acid sequence or premature protein truncation.

Transcription Process

  • Occurs in the nucleus.
  • Enzymes (helicases and topoisomerases) unwind DNA.
  • RNA polymerase transcribes DNA template into hnRNA (heterogeneous nuclear RNA).
  • hnRNA undergoes post-transcriptional modifications:
    • Splicing: Removal of introns, ligation of exons by spliceosome.
    • 5′ Cap: 7-methylguanylate triphosphate cap added to protect mRNA.
    • 3′ Poly-A Tail: Polyadenylation to stabilize mRNA and assist ribosome binding.

Translation Process

  • mRNA exits nucleus, binds to ribosome in cytoplasm.
  • Initiation: Small ribosomal subunit binds mRNA, large subunit joins after initiator tRNA (methionine) binds to start codon.
  • Elongation: Ribosome moves along mRNA, adding amino acids to polypeptide chain.
    • A site: Holds incoming tRNA-amino acid complex.
    • P site: Holds growing polypeptide chain.
    • E site: Where inactive tRNA pauses before exiting ribosome.
  • Termination: Ribosome reaches stop codon, release factors terminate translation, releasing polypeptide.

Post-Translational Modifications

  • Proteins undergo additional modifications:
    • Phosphorylation: Adds phosphate groups.
    • Carboxylation: Adds carboxylic acid groups.
    • Glycosylation: Adds oligosaccharides.

Gene Expression Control

Prokaryotes

  • Operons: Cluster of genes with a single mRNA transcription.
    • Inducible Systems: Repressor binds to operator, blocking RNA polymerase until induced (e.g., Lac operon).
    • Repressible Systems: Transcription constant until repressor and corepressor complex inhibits transcription (e.g., Trp operon).

Eukaryotes

  • Transcription Factors: Bind specific DNA sequences to regulate expression.
    • Promoters: Near start site (within 20 base pairs).
    • Enhancers: Distant from start site (more than 25 base pairs).