IAS01,02

IAS01: Genes, RNA and Proteins

• visualize transcription, splicing and translation mechanisms central to molecular biology

The Central Dogma: transcription, translation (DNA → RNA → protein)
More recently: reverse transcription (RNA → DNA), enzymes that add epigenetic marks (protein → DNA), replication of RNA (in virus), etc.

B-DNA

• most common conformation
• right-handed helix (clockwise as it goes forward)
• major groove (long gap), minor groove (short gap)
• ribose & phosphate along outside
• bases in the middle
• Chargaff's Rule: amount of A = T, G = C
• purines: A, G; pyrimidines: T, C

Transcription

• from 5' to 3'

• Initiation

  1. TATA-box binding protein bind to DNA
  2. other components of TFII, RNA polymerase II bind
  3. transcription factors at cis-acting enhancers can trigger elongation

• Elongation

• Termination

Splicing

• pre-mRNA before splicing
• removes introns by using spliceosome (set of proteins)
• Spinal muscular atrophy is an inherited disease caused by splicing problems

Translation

sequence that tRNA binds at ribosome: A site → P site → E site

IASM02: Molecular Biology and its Relevance to Medicine

• illustrate how problems in transcription and translation can lead to disease through specific examples

Sickle cell disease

caused by defects in haemoglobin

Haemoglobin

• tetramer (4 subunits), α2β2 structure
• α protein subunit HBA2 coded by HBA1, HBA2 genes
• β protein subunit HBB1 coded by HBB gene
  (human genes--italic caps, protein--non italic)

sickle cell HBB gene: glutamic acid (hydrophilic side chain) → valine (hydrophobic side chain)
→ sickle cell haemoglobin tends to form fibres due to interactions between beta chains
→ distortion of cell shape → disrupted function

persistence of sickle cell anaemia: heterozygous advantage → selection pressure for HbS to be maintained in population

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other examples:
Thalassaemia
cystic fibrosis
mutation in CFTR

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