DNA Translation

Learning Outcomes

  • Describe genetic code context (codons and amino acids).

  • Stages of translation: initiation, elongation, termination.

  • Effects of phosphorylation on protein activity, function, localization.

  • Importance of regulating protein levels and forms of post-translational modification.

Key Steps in Information Processing

  • Transcription: DNA to mRNA.

  • Translation: mRNA to protein (amino acids).

Translation Components

  1. mRNA: Template encoding protein information.

  2. tRNA: Carrier, brings amino acids to mRNA.

  3. rRNA: Structural and functional roles in ribosome.

  4. Ribosomal proteins.

  5. Release/termination factors.

Genetic Code and Codons

  • Codon: 3 nucleotides coding for 1 amino acid.

  • 64 possible codons from 4 nucleotides.

  • AUG codon initiates protein synthesis coding for methionine.

Open Reading Frame (ORF)

  • Continuous codon sequence between initiation and termination codons.

Characteristics of Genetic Code

  • Specific, universal, redundant, and non-overlapping.

Mutations and Disease Examples

  • Codon amplification may lead to diseases (e.g., Huntington's).

  • Sickle Cell Anemia from a missense mutation in the β-globin gene.

Transfer RNA (tRNA)

  • Cloverleaf structure with anticodon for mRNA.

  • Wobble pairing allows flexibility in matching codons.

Ribosome Structure and Function

  • Sites: A (Aminoacyl), P (Peptidyl), E (Exit).

  • Ribosome assembles tRNA and mRNA for amino acid translation.

Process of Translation

Initiation

  • Assembly of ribosomal units, mRNA, and tRNA.

  • Recognition of start codon by tRNA (AUG).

Elongation

  1. Aminoacyl-tRNA arrives at A site.

  2. Peptide bond formation between amino acids.

  3. Ribosome translocates, moving the chain.

Termination

  • Stop codon in A site triggers release factor, disassembling complex.

Dynamic Regulation of Protein Activity

  • Influenced by transcription/translation rates, degradation, and localization.

Protein Degradation Mechanisms

  1. Lysosomal: For imported proteins.

  2. Proteasomal: For cytosolic proteins marked by polyubiquitination.

Post-Translational Modifications (PTMs)

  • Include phosphorylation, ligand binding, cleavage, ubiquitination.

Phosphorylation Mechanism

  • Adds phosphate to serine, threonine, tyrosine residues.

  • Alters protein localization, function, and degradation markers.

Kinases as Therapeutic Targets

  • Example: Gleevec for Chronic Myelogenous Leukemia targeting BCR-ABL fusion kinase.