Influencing Iron Homeostasis by Transition Metal Complexes Interacting with a messenger-RNA Stem Loop in the Iron Regulating Element

Abstract

The maintaining of the precise regulation of iron homeostasis is fundamental to assure cells viability. In this context the interplay between the messenger RNA Iron Response element (IRE) and the iron response protein 1 (IRP1) is crucial to regulate the expression of ferritin and hence the level of labile free iron pool. We have shown, using a combination of molecular modeling and experimental techniques, that tris bipyridine iron complexes (AIM3) interact specifically with the IRE RNA stem-loop in solution, without inducing noticeable structural deformations. Furthermore, we have also shown that, at a cellular level, this interaction may be traced back to the downregulation of ferritin translation, probably due to the stabilization of the IRE stem-loops thus favoring its binding to IRP1 or by inhibiting the downstream recruitment of ribosomal subunits.