Nancy L. Greenbaum, Ph.D.
Professor - Structural Biology of RNA
1305B HN (tel 212-772-5354), lab 1305C HN (tel 212-772-4284), fax (dept) 212-772-5332, email email@example.com,
Ph.D. University of Pennsylvania, Postdoc Rockefeller University and Columbia University
As the major research focus of our laboratory, we attempt to answer questions about how RNA molecules fold and interact with other RNA, metal ions, and proteins in order to carry out the complex activity of precursor messenger (pre-m)RNA splicing. This process, by which noncoding sequences of pre-mRNA molecules, or introns, are excised, and flanking coding regions, or exons, are ligated together, is an essential step in preparation of mRNA transcripts prior to translation of their message into protein sequences.
Pre-mRNA splicing in eukaryotic (compartmentalized) cells is performed within the nucleus by a dynamic supremolecular assembly called the spliceosome, which comprises five recyclable small nuclear (sn)RNA molecules and a large number (>150) of associated proteins. By comparison, the same splicing chemistry is carried out in a number of prokaryotic organisms and organelles of eukaryotic organisms by a simpler system, called a Group II intron, in which part of the RNA intron itself folds into a six-domain structure to excise itself without the need for proteins. Limited areas of resemblance between the spliceosome and Group II intron have fueled speculation of a shared evolutionary ancestry and the likelihood that the spliceosomal reaction is also catalyzed by its RNA components. Using a combination of biochemistry, biophysical, and spectroscopy techniques, we are pursuing several lines of investigation that contribute to our overall understanding of the structural biology of pre-mRNA splicing in the two systems.
1. Yuan, F., Griffin, L., Phelps, L., Buschmann, V., Weston, K., and Greenbaum, N.L. (2007) Use of a novel Förster resonance energy transfer method to identify locations of site-bound metal ions in the U2-U6 snRNA complex. Nucleic Acids Res. 35, 2833-2845.
2. Jennings, T.L., Schlatterer, J.C., Greenbaum, N.L., and Strouse, G.F. (2006) NSET molecular beacon analysis of hammerhead RNA substrate binding and catalysis. Nano Lett. 6, 1318-1324.
3. Schlatterer, J.C., Crayton, S.H., and Greenbaum, N.L. (2006) Conformation of the Group II Intron Branch Site in Solution. J. Am. Chem. Soc. 128, 3866-3867.
4. Schroeder, K., Skalicky, J.J., and Greenbaum, N.L. (2005) NMR spectroscopy of RNA duplexes containing pseudouridine in supercooled water. RNA 11, 1012-1016.
5. Xu, D., Greenbaum, N.L., and Fenley, M.O. (2005) Solvent accessible surface area and electrostatic surface potential of the spliceosomal branch site helix. Nucleic Acids Res. 33, 1154-1161.
6. Newby, M.I., and Greenbaum, N.L. (2002) Investigation of Overhauser effects between pseudouridine and water protons in RNA helices. Proc. Natl. Acad. Sci. 99, 12697-12702.