A tale of two metals: Zinc in RNA binding Zinc Fingers and Iron in Nanomedicine

Metal ions play key roles in biology and are also utilized as pharmaceuticals to perturb biological systems. In the former area, we are studying the role of zinc in RNA regulation. We are focusing on two CCCH type Zinc Finger Proteins (CCCH ZFs): Tristetraprolin (TTP) and Cleavage and Polyadenylation Specificity Factor 30 (CPSF30). TTP plays a central role in regulating inflammation, while CPSF30 regulates pre-mRNA processing and is a target of the human influenza virus protein. Our efforts to characterize the biochemical mechanisms of metal mediated RNA recognition by these proteins, along with cellular studies to tease out the roles of the metal ions in RNA processing will be presented. In the latter area, iron nanoparticles are used clinically to treat iron deficient anemia; however, the fate of these nanoparticles is not understood and there are some reports of toxicity in patients. We have developed a bioanalytical assay that couples liquid chromatography with Inductively Coupled Plasma Mass Spectrometry (LC-ICP-MS) that allows us to track the fate of iron nanoparticle drugs in blood plasma while simultaneously measuring iron speciation. We are applying this assay to a clinical trial healthy volunteers, and our initial findings regarding the fate of iron nanoparticles in humans will be presented.