Metallobiochemistry of RNA: Mg(II) and Fe(II) in divalent binding sites

RNA;RNA-ion interactions;Magnesium;Iron;Circular dichroism;Quantum mechanics;Electron transfer;RNA catalysis;RNA world hypothesis

Okafor, Chiamaka Denise ; Hud, Nicholas V Williams, Loren D. Chemistry and Biochemistry Kelly, Wendy L. Oyelere, Adegboyega K. Wartell, Roger M. ; Hud, Nicholas V

University:Georgia Institute of Technology

Department:Chemistry and Biochemistry

关键词: RNA;    RNA-ion interactions;    Magnesium;    Iron;    Circular dichroism;    Quantum mechanics;    Electron transfer;    RNA catalysis;    RNA world hypothesis;   

Others  :  https://smartech.gatech.edu/bitstream/1853/53904/1/OKAFOR-DISSERTATION-2015.pdf

美国|英语

来源: SMARTech Repository

【 摘 要 】

Cations are essential for ribonucleic acids (RNA), as they neutralize the negatively charged phosphate backbone. Divalent metals play important roles in the folding and function of RNA. The relationship between RNA and divalent cations magnesium (Mg(II)) and iron (Fe(II)) has been investigated. Mg(II) is involved in tertiary interactions of many large RNAs, and necessary for ribozyme activity.The influence of Mg(II) on RNA secondary and tertiary structure is investigated experimentally. Mg(II) binding to A-form RNA is accompanied by changes in CD spectra, indicating that Mg-RNA interactions influence the helical structure of RNA duplexes and helical regions of unfolded RNAs. Quantum mechanics calculations are used to probe the energetics of Mg(II)-chelation with phosphate oxygen atoms of nucleic acids. We identify the specific forces that contribute to stability of Mg(II)-chelation complexes in RNA.Fe(II) can serve as a substitute for Mg(II) in RNA folding and function. Fe(II) was abundant on early earth, it is plausible that RNA folding and function was mediated by Fe(II) instead of, or in combination with, Mg(II) in the anoxic environment of early earth. We have investigated oxidoreductase catalytic activity observed in RNA when in combination with Fe(II).This activity, only observed in the presence of Fe(II) and absence of Mg(II)appears to be a resurrection of ancient RNA capabilities that were extinguished upon the depletion of Fe(II) from the environment during the rise of oxygen after the great oxidation event. Finally, metal-ion based cleavage of RNA is used to identify the binding sites of Mg(II) and Fe(II).We observe that both metals cleave RNA in similar positions, providing further support for Fe(II) as a substitute for Mg(II) in RNA.