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

other examples: Thalassaemia cystic fibrosis mutation in CFTR