Control of Gene Expression (cytosol)

• ferritin is responsible for iron storage inside the cell
• increase in iron level, there will be an increase in production of ferritin
• Ferritin regulation is mediated by iron regulatory proteins (IRPs) and it targets the iron response element (IRE)

  • absence of iron: repressing the translation
  • presence of iron: allowing translation of ferritin
• eIF - elongation initiation factors
• Translation regulatory control involving miRNA:

  miRNAs form mismatches duplexes (dsDNA) with sequences within the 3’ untranslated region (UTR) of their target mRNA thus repressing translation and targeting the mRNA for degradation by stimulating deadenylation
• Lipidation: modulates the function of targeted proteins by increasing their binding affinity to biological membranes, rapidly switching their subcellular localizations, affecting folding and stability, and modulating association with other proteins
• Glycosylation: the process of adding carbohydrates
• The proteins to which carbohydrate chains have been added are called glycoproteins
• protein kinases phosphorylate either serine and threonine or tyrosine residues
• Protein phosphorylation is reversed by protein phosphatases
• Phosphorylation: plays critical roles in the regulation of many cellular processes, including cell cycle, growth, apoptosis and signal transduction pathways
• Ubiquitination: process through which ubiquitin molecules are attached to protein substrates for protein degradation, it regulates various cellular processes, including immune response, angiogenesis, cell proliferation, apoptosis, and DNA repair
• Ubiquitination:

  • E1 - ubiquitin-activating enzyme
  • E2 - ubiquitin-conjugating enzyme
  • E3 - ubiquitin-protein ligase
• Shine-Dalgarno sequence is found upstream of the initiating AUG codon where the ribosome starts scanning the mRNA
• Shine-Dalgarno sequence allows bacterial cells to regulate gene expression through translational control
• antisense RNA: non-coding strand that inhibit translation by competing with ribosomes for translation initiation regions (TIRs) on nascent mRNA
• Shine-Dalgarno sequence:

  • Attachment of translation repressor protein to AUG - OFF
  • Increase in temperature - ON
  • Addition of small molecule in between hairpin loops - OFF
  • Usage of antisense RNA - OFF
• lac operon: enzyme that catalyzes the cleavage of lactose (β-galactosidase) and other enzymes involved in lactose metabolism
• lactose metabolism involves the products of two other closely linked genes:

  • lactose permease - which transports lactose into the cell
  • transacetylase - which is thought to inactivate toxic thiogalactosides that are transported into the cell along with lactose by the permease
• Leaky scanning leads to the production of closely related proteins that differ only in their amino termini

  • can frameshift
  • can lead to miss out of AUG (first)
• Internal Ribosome Entry Site (IRES) provides opportunity for translational control in eukaryotes and viruses
• IRES is typically several hundred nucleotides in length and folds into specific structure that binds many proteins involved in the 5'cap-dependent translation process
• • mRNAs in eukaryotes are more stable
  • bacterial RNAs are easily degraded by exonucleases
• Lac Z - Galactosidase

  • breaks down lactose

  Lac Y - Galactoside permease

  • brings lactose to member transport

  Lac A - Transacetylase

  • inactivates toxic compound
• operator - negative regulatory site of the lac operon
• Catabolite activator protein (CAP) - positive regulatory site for the expression of lac operon
• Prokaryotic Translational Control

  A) translation repressor protein

  B) protein made

  C) On

  D) Off

  E) increased temperature

  F) Off

  G) On

  H) On

  I) Small molecule

  J) Off

  K) Antisense RNA

  L) On

  M) Off