An iron-responsive element type II in the 5′-untranslated region of the Alzheimer's amyloid precursor protein transcript

Abstract

Iron-responsive elements (IREs) are the RNA stem loops that control cellular iron homeostasis by regulating ferritin translation and transferrin receptor mRNA stability. We mapped a novel iron-responsive element (IRE-Type II) within the 5′-untranslated region (5′-UTR) of the Alzheimer's amyloid precursor protein (APP) transcript (+51 to +94 from the 5′-cap site). The APP mRNA IRE is located immediately upstream of an interleukin-1 responsive acute box domain (+101 to +146). APP 5′-UTR conferred translation was selectively down-regulated in response to intracellular iron chelation using three separate reporter assays (chloramphenicol acetyltransferase, luciferase, and red fluorescent protein ..