Iron and zinc co-factored metalloproteins perform a variety of functions including providing structural integrity, aiding in transport and storage, and engaging in enzymatic activity. One important group of metalloproteins are zinc finger (ZF) proteins. In this thesis, I investigate two RNA-binding ZFs to understand both structural and functional aspects and aim to highlight their importance in biology. The cleavage and polyadenylation specificity factor 30 (CPSF30) is a non-classical ZF containing five CCCH-type and one CCHC-type ZF domains that binds RNA targets. One of CPSF30’s CCCH ZF domains can bind a 2Fe-2S cluster; however, the role of this cluster is poorly understood. RNA binding assays on CPSF30 determined that the CCCH domains bind AU-rich RNA and the CCHC domain binds U-rich RNA. Metal-catalyzed oxidation – mass spectrometry (MCO-MS) identified the site of the 2Fe-2S cluster as the second CCCH domain. Additional EPR and Mössbauer spectroscopies demonstrated the 2Fe-2S cluster is redox active, however, the redox activity doesn’t affect RNA binding. I characterized individual CCCH-type maquettes of CPSF30 to determine if Fe-S cluster binding can occur in the other domains. Not only can each individual domain load an Fe-S cluster as confirmed by UV-Vis and XAS, but the clusters are redox active, as confirmed by EPR. Another non-classical ZF is the Ran-binding domain containing protein 2 (ZRANB2). ZRANB2 contains two CCCC-type ZF domains and functions to bind RNA, interact with other proteins, and participate in alternate splicing. I determined the effect of zinc binding on ZRANB2 conformation and analyzed protein dynamics with RNA utilizing UV-Vis, CD, fluorescence assays, and HDX-MS. ZRANB2 is found to be persulfidated in a variety of cell lines when measured by persulfide specific proteomics. I demonstrate that isolated ZRANB2 is persulfidated by H2S in a Zn and O2 dependent manner via an in situ dimedone switch tagging method. Superoxide was determined to be an intermediate of the persulfidation reaction and persulfidation abrogated RNA binding. I proposed that this modification is linked to regulation of the spliceosome. Lastly at the end of my thesis, through a variety of techniques, I analyze the physicochemical properties of FDA-approved iron nanoparticle drug, Monoferric.