Faculty

Martha Fedor 
Associate Professor
CHEMICAL PHYSIOLOGY
TSRI - 1997

Joint Appointments 
The Skaggs Institute for Chemical Biology

Education 
B.S., University of Michigan, Ann Arbor, 1976, Zoology

Ph.D., University of California, Berkeley, 1982 , Molecular Biology

Awards & Activities 
Member of the Board of Directors of the RNA Society, 2000-2001

Research Focus 
Mechanisms of RNA Assembly and Catalysis

Understanding mechanisms of RNA catalysis remains an intriguing challenge, one that has grown in significance since the recent demonstration that the ribosome is an RNA enzyme. Our research focuses on one catalytic RNA, the hairpin ribozyme, which cuts and rejoins its RNA substrates. Unlike other ribozymes that recruit metal cation cofactors to perform catalytic chemistry, the hairpin ribozyme uses functional groups within the RNA itself to carry out catalysis. We use enzymological, structural and biochemical methods to learn how specific functional groups in the hairpin active site contribute to catalysis. RNA catalysis provides a sensitive, quantitative signal that an RNA has assumed its functional structure making ribozymes, particularly fruitful systems for RNA structure-function studies. Quantitative enzymological studies of ribozymes have led to remarkably detailed insights into the structural transitions that comprise RNA assembly and reaction pathways and defined how interactions with other molecules influence these pathways in vitro. However, the complexity of biological reactions and the lack of information about the intracellular environment limit the accuracy with which in vitro reactions can recapitulate biology. We have devised a way to quantify ribozyme reaction kinetics in yeast in order to learn how principles of RNA folding and catalysis that have been revealed through in vitro studies relate to the behavior of RNAs in living cells. Insights gained from our studies will facilitate the design of ribozymes for therapeutic applications and shed light on more complex RNA-mediated reactions in gene expression.

Selected References 
Kuzmin, Y.I., Da Costa, C.P., and Fedor, M.J. Role of an Active Site Guanine in Hairpin Ribozyme Catalysis Probed by Exogenous Nucleobase Rescue, J. Mol. Biol., 340(2), 233-251. 2004

Fedor, M.J. and Williamson, J.R. The catalytic diversity of RNAs. Solicited review. Nat. Rev. Mol. Cell Biol. 6, 399-412. 2005

Kuzmin, Y.I., Da Costa, C.P., Cottrell, J.W. and Fedor, M.J. Role of an Active Site Adenine in Hairpin Ribozyme Catalysis. J. Mol. Biol. 349, 989-1010. 2005.

Mahen, E.M., Harger, J.H., Calderon, E.M., and Fedor, M.J. Kinetics and Thermodynamics make Different Contributions to RNA Folding In Vitro and In Yeast. Mol. Cell. 19, 27-37. 2005