Associate Professor, Center for RNA Molecular Biology (Faculty since 1996)

Education: Ph.D.: Department of Biochemistry, University of Alabama at Birmingham

Post-doc: Department of Biology, Indiana University

Secondary Appointment in: Department of Biochemistry

Email: meh2

Office Location: Wood Blgd. W106

Office Phone: 216-368-4779

Office FAX: 216-368-2010

Laboratory Location: W103

Laboratory Phone: 216-368-0381

Curriculum Vitae

RNase P is a ribonucleoprotein enzyme with a catalytic RNA subunit that depends on a small protein cofactor for molecular recognition. Thus, it serves as a facile model system to explore fundamental aspects of molecular recognition, RNA-protein interactions and RNA-metal ion interactions. We are pursuing these lines of investigation using the standard physical and spectroscopic tools as well as developing new approaches including collaborative efforts at application of kinetic isotope effects (with Vernon Anderson) and Raman spectroscopy (with Paul Carey).

Two of the fundamental questions for both RNA and protein enzymes that catalyze phosphoryl transfer are “What is the mechanism of the reaction?” and “How do active site functional groups influence the chemical bonding of the substrate to achieve catalysis?” Both the chemical mechanism and active site interactions influence the bonding environment of the atoms undergoing reaction, which can be assessed by measuring the effects of isotopic substitution at these positions. An important outgrowth of our collaborative studies of ribozyme catalysis has been the development of methods to determine isotope effects for enzymatic and non-enzymatic phosphoryl transfer reactions involving RNA. These studies promise to provide important new information on the mechanism of RNA catalyzed reactions and tests of current hypotheses concerning the role of specific active site interactions.

Pubmed Link to Publications

Select Publications

Zahler, N.H. and Harris, M.E. (2004). “Site-Specific Modification of RNA” ” in Handbook of RNA Biochemistry, Wiley. Hartmann, Binderief, Shon and Westhof, eds.

Harris, M.E. and Christian, E.L. (2004). “Probing RNA Structure by Photoaffinity Crosslinking With 4-Thiourine and 6-Thioguanosine” in Handbook of RNA Biochemistry, Wiley. Hartmann, Binderief, Shon and Westhof, eds.

Zahler, N.H., Sun, L., Christian, E.L. and Harris, M.E. (2005). The pre-tRNA nucleotide base and 2'-hydroxyl at N(-1) contribute to fidelity in tRNA processing by RNase P. J. Molec. Biol. 345(5):969-85.

Anderson, V.E., Harris ME and Cassano AG (2006) “Nucleophile Isotope Effects” in Isotope Effects in Chemistry and Biology. CRC Press. Kohen A, Limbach H-H (eds)

Anderson, V.E., Ruszczysky, M. and Harris, M.E. (2006). Nucleophilic activation in enzyme catalysis. Chem. Rev. 106(8):3236-51.

Guo X, Campbell FE, Christian EL, Anderson VE and Harris ME. (2006) RNA-dependent folding and stabilization of C5 protein during assembly of the E. coli RNase P holoenzyme. J. Molec. Biol. 360(1):190-203

Christian EL, Johnson, K, Perrera, N and Harris, ME (2006). Evidence for a role for the P4 metal binding site in enhancing catalytic metal ion affinity by substrate positioning. RNA 12(8):1463-7.

Sun L, Campbell FE and Harris ME (2006) Substrate specific effects of C5 protein lead to uniformity in binding and catalysis by RNase P. EMBO J. 25(17):3998-4007

Harris ME and Anderson VE (2007) “Chemistry of Natural Ribozymes”. Encyclopedia of Chemical Biology. Wiley.

Sun L and Harris ME (2007). Binding of C5 protein to the P RNA ribozyme increases catalytic rate by influencing active site metal ion affinity. RNA 34:1-11.

Cassano AG, Wang B, Anderson DR, Previs S, Harris ME, Anderson VE. (2007). Inaccuracies in selected ion monitoring determination of isotope ratios obviated by profile acquisition: nucleotide 18O/16O measurements. Anal. Biochem. 367(1):28-39.

Dai, Q, Frederiksen, J, Anderson VE, Harris ME, and Piccirilli, J (2008) Efficient synthesis of 2'-[18O]-uridine and its incorporation into oligonucleotides: A new tool for mechanistic studies of phosphoryl transfer reactions by isotope effect analyses. J. Org. Chem. 73(1):309-11

Harris, ME and Christian EL (2008) Understanding the Role of Metal Ions in RNA Folding and Function: Lessons from RNase P, a Ribonucleoprotein Enzyme. In Biophysics of Non-protein Encoding RNAs. Springer, Inc.

Schroeder LA, Gries TJ, Saecker RM, Record T, Harris ME, and deHaseth P (2008) Tyrosine-adenine stacking and an open intermediate in RNA polymerase - promoter complex formation. J. Molec. Biol. in press

Harris ME and Cassano AG (2008) Experimental analysis of ribozyme chemical dynamics. Curr. Op. Chem Biol. in press.