CSB349H1 Lecture Notes - Lecture 13: Iron Response Element, Upstream Open Reading Frame, Ferritin
14 May 2018
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Lecture 13(a): Translational & Post-Translational Regulation
Translational Control Sites:
• 3’ and 5’ UTR both play an important role in translational control
Iron Homeostasis:
• Two different proteins that play important roles in iron levels within cells:
o Ferritin:
§ Has iron response element (IRE) in its 5’ UTR mRNA transcript
§ Functions to store iron when iron levels are high
o Transferrin Receptor (TfR):
§ Has iron response element (IRE) in its 3’ UTR mRNA transcript
§ Functions to uptake iron from the extracellular environment into the cell
• Iron Regulatory Protein (IRP) has two functions within the cell that regulates the levels of
ferritin and TfR:
a) High Iron Levels:
§ Iron found in the iron core of IRP will have enzymatic function and will
convert citrate into iso-citrate (aconitase)
b) Low Iron Levels:
§ Iron found in the iron core will dissociate and IRP no longer has enzymatic
function and becomes an RNA binding protein
• IRP will bind to the 5’ IRE of ferritin and block translation
• IRP will bind to the 5’ IRE of TfR and induce translation
ð When we have a higher influx of iron in the cell; iron will bind to IRP and convert it back
replenish its enzymatic function; will be removed from UTRs and ferritin translation increases
Upstream Open Reading Frames (uORFs):
• Many genes have an upstream open reading
frame – there is additional start codons found in the 5’ UTR however they are out of frame
o uORF often encode small peptides that can affect the translation of the transcript;
function to repress translation
§ Mutated uORF results in higher levels of transcript translation = more protein
•
HR
gene consists of 4 uORF – mutation of the 2nd uORF leads to hairlessness
o 2nd uORF code for a small peptide that is conserved between many species
• Experiment:
o 5’ UTR of the HR gene was fused to a reporter gene (GFP) – expression of the gene
increased significantly if the 2nd uORF was mutated
§ Small peptide that is expressed by the 2nd uORF (normal conditions) functions
to bind to the ribosome and reduce translation of the gene
Document Summary
Translational control sites: 3" and 5" utr both play an important role in translational control. Iron homeostasis: two different proteins that play important roles in iron levels within cells, ferritin: Has iron response element (ire) in its 5" utr mrna transcript. Functions to store iron when iron levels are high: transferrin receptor (tfr): Has iron response element (ire) in its 3" utr mrna transcript. Functions to uptake iron from the extracellular environment into the cell: iron regulatory protein (irp) has two functions within the cell that regulates the levels of ferritin and tfr, high iron levels: Iron found in the iron core of irp will have enzymatic function and will convert citrate into iso-citrate (aconitase: low iron levels: Iron found in the iron core will dissociate and irp no longer has enzymatic function and becomes an rna binding protein. Irp will bind to the 5" ire of ferritin and block translation.
