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Thermodynamic Implications of Metal‐RNA Interactions: Analyzing Metal Binding to TAR RNA
Author(s) -
Booth David Scott,
FerrinO’Connell Ian O’Brien,
Grover Neena
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a68-d
Subject(s) - rna , metal ions in aqueous solution , tar (computing) , metal , chemistry , magnesium , titration , folding (dsp implementation) , crystallography , inorganic chemistry , biochemistry , organic chemistry , computer science , gene , programming language , electrical engineering , engineering
Metal ions are important co‐factors in RNA stabilization, folding and catalysis. In each of these roles, it is expected that the number and type of interactions between metal ions and RNA lead to a particular thermodynamic value. The crystal structure of t rans‐ a ctivating r esponse (TAR) element of HIV‐1 RNA shows inner‐sphere interactions with three calcium ions at the trinucleotide bulge region. Thus, it can be used as a model to measure thermodynamic contributions for specific metal‐RNA interactions. Using thermal denaturation experiments we show that calcium and magnesium can stabilize TAR RNA by an additional 1–2 kcal/mole over 1M KCl. Upon titration with small concentrations (1–10 mM range) of metal ions, a 3–5 kcal/mole change in ΔG is observed, which indicates specific interactions between metal ions and TAR RNA. A similar analysis of other bulge sequences is being performed to allow us to determine sequence specificity of these interactions and to provide ΔG for non‐specific interactions.