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J. Lawrence Oncley Collegiate Professor of Chemistry and Biophysics

• About

  For a long time, it was believed that RNA would only assume the roles of transfer, ribosomal and messenger RNA in protein biosynthesis. Composed of only four chemically similar nucleotides, it was assumed that RNA lacked the ability to fold into complex three-dimensional structures needed to effect diverse functions. Although we now know that the role of RNA function in gene expression and regulation goes well beyond protein biosynthesis, the current repertoire of RNA structures has by and large vindicated original expectations; RNA does have a limited structural coverage. What then is the origin of RNAs functional versatility?
  Unlike many proteins, RNAs functional versatility does not appear to derive principally from its structure, but rather from its ability to undergo conformational change. Dynamical changes in RNA conformation are now implicated in almost every known RNA function, including in the function of the ribosome, spliceosome, catalytic ribozymes, messenger and viral RNAs, and small interfering RNAs. The next frontier in the structural biology of RNA is therefore the characterization of functional dynamics at atomic resolution.

  A primary objective of our research program is to develop novel NMR methodology for characterizing RNA dynamics with high structural and temporal resolution. These methods uniquely provide an atomic time-resolved description of RNA dynamics. A second objective is to apply these high resolution dynamical methods to understand how motions contribute to the functions of RNA domains derived from the untranslated 298 nt leader RNA located at the 5'-end of the HIV-1 genome. A third objective is to gain insight into dynamical principles that can aid the rational design of RNA binding anti-HIV therapeutics.

  Representative Publications

  Carroll, E. C., White, J. L., Florean, A. C., Bucksbaum, P. H., and Sension, R. J. “Multiphoton Control of the 1,3-Cyclohexadiene Ring-Opening Reaction in the Presence of Competing Solvent Reactions”  Feature Article, Journal of Physical Chemistry A, v112 (30) 6811-6822.

  Harris, D. A., Stickrath, A. B., Carroll, E. C., and Sension, R. J., 2007, “The influence of environment on the electronic structure of cob(III)alamins: Time-resolved absorption studies of the S1 state spectrum and dynamics.” Journal of the American Chemical Society, v129 (24) 7578-7585.

• Education

  • Ph.D., Yale University

• Research Areas of Interest

  • Structure and dynamics of nucleic acids and ribonucleoproteins using NMR spectroscopy

• Selected Publications:

• Articles

  • (2012) Unraveling the structural complexity in a single stranded RNA tail: Implications for efficient ligand binding in the prequeuosine riboswitch, Nucleic Acids Research
  • (2010) NMR and XAS reveal an inner-sphere metal binding site in the P4 helix of the metallo-ribozyme ribonuclease P, Proc. Natl. Acad. Sci.
  • (2006) Insight into the CSA Tensors of Nucleobase Carbons in RNA Polynucleotides From Solution Measurements of Residual CSA: Towards New Long-Range Orientational Constraints, Magnetic Resonance
  • (2006) Resolving the Motional Modes that Code for RNA Adaptation, Science
  • (2005) Dynamics-Based Amplification of RNA Function and its Characterization By Using NMR Spectroscopy, ChemBioChem
  • (2005) Electrostatic interactions dictate the ligand-induced arrest of RNA global motions, Chem. Int. Ed.
  • (2003) Probing motions between equivalent RNA domains using magnetic field induced residual dipolar couplings, Am. Chem. Soc.