Regulation of transcription and translation

Question 1

what are transcriptional factors

Answer 1

• Transcription factors are proteins
• Move from cytoplasm → nucleus
• Bind to DNA at a specific DNA base
  sequence on a promotor region
  (near start / upstream of target
  gene)
• Stimulate (‘activator’) or inhibit
  (‘repressor’) transcription (the
  production of mRNA) of target
  gene(s) (by helping or preventing
  RNA polymerase binding)

Question 2

what is The role of oestrogen in initiating transcription

Answer 2

1. Oestrogen, a steroid hormone, can diffuse across the phospholipid bilayer of the cellsurface membrane as it’s lipid soluble.
2. In cytoplasm, oestrogen binds to a
   receptor of an inactive
   transcription factor, forming a
   hormone-receptor complex
3. Inactive transcription factor
   changes shape, resulting in active
   transcription factor
4. Diffuses from cytoplasm into
   nucleus and binds to specific DNA
   base sequence on a promotor
   region
5. Stimulates transcription of genes
   by helping RNA polymerase to bind

Question 3

what is a nucleosome

Answer 3

DNA wrapped around histone proteins
* How closely the DNA and histone are packed together affects transcriptiom

Question 4

what is epigentics

Answer 4

heritable changes in gene function (expression) without changes to the base
sequence of DNA, caused by changes in the environment

Question 5

how can epigentics inhibit transcription

Answer 5

Methylation of DNA
* Methyl groups added to cytosine bases in DNA
* Nucleosomes pack more tightly together → prevents transcription
factors binding; genes not transcribed (RNA polymerase can’t bind)
* Irreversible

Decreased acetylation of associated histones
* Decreased acetylation of increases positive charge of histones
* Histones bind DNA (which is negatively charged) more tightly →
preventing transcription factors binding; genes not transcribed
* Reversible

Question 6

what is the relevance of epigenetics on disease development and treatment, especially cancer

Answer 6

• Epigenetic changes that increase the expression of an oncogene, or that silence a
  tumour suppressor gene, can lead to tumour development (see next section)
• Tests can be used to see if a patient has abnormal levels of methyl and acetyl – early
  indicator of cancer (called a biomarker)
• Could be manipulated to treat cancer i.e. drugs to prevent histone acetylation / DNA
  methylation that may have caused these genes to be switched on/off, resulting in cancer

Question 7

what is RNA interference (RNAi)

Answer 7

RNA molecules inhibit translation of mRNA produced by
transcription

• RNAi can be moderated by either siRNA or miRNA (subtle differences between the two)
  1. Micro-RNA (miRNA)
• Formed as hair-pin bends of RNA but processed into single-strands 22-26
  nucleotides long, both become incorporated into a protein-based RISC (RNA-induced silencing complex)
  2. Small interfering RNA (siRNA)
• Formed as double-stranded molecules 21-25 bp long, one strand incorporated
  into a protein-based RISC
• Single-stranded miRNA/siRNA within a RISC binds to a molecule of mRNA containing a
  sequence of bases complementary to its own → mRNA hydrolysed / translation stopped
• miRNA expression deregulated in many human diseases including cancer → offer
  opportunities as biomarkers and novel therapies