William Edward Gilbert Professor of Molecular, Cellular and Developmental Biology
Professor of Chemistry
Investigator, Howard Hughes Medical Institute
Member of Yale faculty since 2002
Research RNA has many functions in the cell, from the transfer of genetic information to the catalysis of chemical reactions. Often it is the folded tertiary structure of an RNA, rather than its primary sequence, that is essential for function. Given the ubiquitous role of folded RNA in biology, we have set out to understand some basic principles: What are the building blocks for RNA tertiary structure and how is RNA energetically stabilized? What are pathways for reaching the folded state? How are RNA and ribonucleoprotein assemblies actively folded and unfolded by RNA remodeling enzymes such as helicases? How can computational and experimental tools be combined to better understand these problems? Many of our studies focus on self-splicing group II introns, which are large ribozymes and mobile genetic elements. Using a combination of biophysical and chemogenetic techniques, we are studying the structures of group II introns and their folding intermediates, determining the energetic contribution of individual tertiary interactions, and monitoring the dynamic behavior of intermediates along the RNA folding pathway. In complementary studies, we examine the role of proteins in RNA tertiary folding and disassembly. We are particularly interested in the chemical mechanism of molecular motor proteins that couple ATP hydrolysis with remodeling of RNA molecules. Experimental work in our laboratory is complemented by the development of new computational approaches for modeling, predicting and analyzing the structures of RNA molecules.
B.A. Princeton University, 1985
Ph.D. Columbia University, 1990
Jane Coffin Childs Postdoctoral Fellow, University of Colorado, 1992
Woodrow Wilson School Program in Science Policy, Princeton University, 1983-1985
Magna cum laude in Chemistry, Princeton University, 1985
J. Malcolm Miller Teaching Award, Columbia University, 1986
Pegram Award, Columbia University, 1989
Jane Coffin Childs Memorial Fund Postdoctoral Fellowship, 1990-1992
Irma T. Hirschl and Monique Weill-Caulier Career Scientist Award, 1992-1997
Searle Scholars Award, 1993-1996
Beckman Young Investigator, 1994-1996
NSF National Young Investigator Award, 1994-1999
Investigator, Howard Hughes Medical Institute, 1997-present
Mayor’s Award for Excellence in Science and Technology, New York, 2002
Member of the American Academy of Arts and Sciences, 2005-present
Editor, Journal of Molecular Biology, 2007-present
Fellow of the American Association for the Advancement of Science, 2007
N. Toor, K.S. Keating, S.D. Taylor, & A.M. Pyle. Crystal structure of a self-spliced group II intron. Science 2008, 320, 77-82.
A.M. Pyle. Translocation and unwinding mechanisms of RNA and DNA helicases. Annu. Rev. Biophys. 2008, 37, 317-336.
M. Roitzsch, O. Fedorova, & A.M. Pyle. The 2’-OH group at the group II intron terminus acts as a proton shuttle to permit reverse splicing. Nat. Chem. Biol. 2010, 6, 218-224.
A.M. Pyle. The tertiary structure of Group II introns: Implications for Biological Function and Evolution. Crit. Rev. Biochem. Mol. Biol. 2010, 45, 215-232.
K.S. Keating & A.M. Pyle. Semiautomated model building for RNA crystallography by using a directed rotameric approach. Proc. Natl. Acad. Sci. USA 2010, 107, 8177-8182.
K.S. Krishanthi, A. Solem, A.M. Pyle, & D. Rueda. Single-molecule analysis of Mss116-mediated group II intron folding. Nature 2010, in press.