BIOA01H3 Lecture Notes - Lecture 13: Iron Response Element, Transferrin Receptor, Ferritin

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14 Aug 2018
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Post-transcriptional regulation of gene expression (Iron-Response Elements)
Translational Regulation
- The most common mechanism of translational regulation affects the initiation process.
- mRNA sequence recognized by binding protein can block ribosome
- mRNA sequence can result in three-dimensional shape that blocks ribosome
Gene Regulation Example: Iron Metabolism
- Iron is essential: humans use ~20 mg/day to make new red blood cells.
- Too much free iron is toxic, too little is bad.
- Cells can safely store iron by binding it to a protein called ferritin. When too much iron.
Free iron can be safely transported to cells in the bloodstream when bound to a protein called
transferrin.
- Transferrin-bound iron is taken into the cells by binding to a cell surface protein called the transferrin
receptor. Too little iron.
Ex. Ferritin is the cytoplasmic iron storage protein that sequesters excess iron when cellular iron levels are too
high. The transferrin receptor is a protein that transports iron from the bloodstream into the cell when iron
levels are too low. Based on this information, a decrease in a cell’s iron levels should ____ ferritin levels and
_____ transferrin receptor levels in a cell.
- Decrease; increase
Elements of Iron Response
- Ferritin: 5’ UTR has a specific shape that allows a protein to bind to it, called iron response element.
- Region is bound by a iron response element binding protein (IRE-BP)
- Transferritin: 3’ UTR structure has instability elements, which don’t translate. IREBP can bind and
block these elements allowing for translation. The IREBP is responsive to iron, it can bind to iron and
change shape, cannot find to transferitin IRE.
Ex 1. Which of the depictions best represents ferritin mRNA under low iron conditions?
- Under low iron conditions, the IRE-BP is active ad bound to the IRE
- When bound to the IRE translation is blocked = no ferritin storage protein is made.
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The most common mechanism of translational regulation affects the initiation process. Mrna sequence recognized by binding protein can block ribosome. Mrna sequence can result in three-dimensional shape that blocks ribosome. Iron is essential: humans use ~20 mg/day to make new red blood cells. Too much free iron is toxic, too little is bad. Cells can safely store iron by binding it to a protein called ferritin. Free iron can be safely transported to cells in the bloodstream when bound to a protein called transferrin. Transferrin-bound iron is taken into the cells by binding to a cell surface protein called the transferrin receptor. Ferritin is the cytoplasmic iron storage protein that sequesters excess iron when cellular iron levels are too high. The transferrin receptor is a protein that transports iron from the bloodstream into the cell when iron le(cid:448)els are too lo(cid:449). Based o(cid:374) this i(cid:374)for(cid:373)atio(cid:374), a de(cid:272)rease i(cid:374) a (cid:272)ell"s iro(cid:374) le(cid:448)els should ____ ferriti(cid:374) le(cid:448)els a(cid:374)d.

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