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Ph.D. (1983) Cornell University
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Eric M. Phizicky
Associate Professor
Contact Information:
- University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, NY 14642
3-7411 Medical Center
Phone: (716) 275-7268
E-Mail: eric_phizicky@urmc.rochester.edu
Research:
tRNA splicing in yeast and vertebrates;
Functional genomics
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tRNA splicing in yeast and vertebrates
We have shown that the last step of tRNA splicing in yeast is
catalyzed by a 2'-phosphotransferase which transfers the splice
junction 2'-phosphate to NAD to form the previously unknown molecule
ADP-ribose 1"-2" cyclic phosphate (Appr>p). We are engaged
in four problems stemming from this work: determining the mechanism
by which substrate is recognized and Appr>p is formed; determining
the fate and cellular role of Appr>p produced during tRNA splicing;
understanding why a fully functional 2'-phosphotransferase homolog
appears to have been present in bacteria for ca. 3 billion years,
despite the fact that bacterial RNAs do not have this type of
intron or the other tRNA splicing enzymes; and investigating why
vertebrates appear to have two seemingly redundant pathways for
splicing tRNA, one of which generates Appr>p.
Functional genomics
We have recently developed a biochemical genomics approach to
identify genes by the activities of their products, together with
S. Fields (U. Washington) and E. Grayhack. To this end, we first
constructed a library of ca. 6000 strains, each of which expresses
a unique yeast ORF as a GST-ORF fusion. To identify genes encoding
different activities, the GST-ORFs are purified in pools, activity
is assayed, and active pools are deconvoluted to determine the
GST-ORF responsible for activity. Using this approach we have
linked three previously unknown gene products with specific biochemical
activities. We are exploring the potential of this biochemical
genomics approach by developing new strategies to expand its versatility
and by continuing to identify new genes encoding different activities.
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RECENT PUBLICATIONS
Martzen, M.R., McCraith, S. M., Spinelli, S. L.,
Torres, F. M., Fields, S., Grayhack, E. J., and Phizicky, E. M.
(1999) A biochemical genomics approach for identifying genes by
the activity of their products. Science 286:1153-1155
Spinelli, S. L., Kierzek, R., Turner, D. H. and
Phizicky, E. M. (1999). Transient ADP-ribosylation of a 2'--phosphate
implicated in its removal from ligated tRNA during splicing in
yeast. J. Biol. Chem. 274:2637-2644.
Spinelli, S. L., Malik, H. S., Consaul, S. A. and
Phizicky, E. M. (1998) A functional homolog of a yeast tRNA splicing
enzyme is conserved in higher eukaryotes and in E. coli. Proc.
Natl. Acad. Sci. USA 95:14136-14141.
Spinelli, S. L., Consaul, S. A. and Phizicky, E.
M. (1997) A conditional lethal yeast phosphotransferase (tpt1)
mutant accumulates tRNAs with a 2'-phosphate and an undermodified
base at the splice junction. RNA 3:1388-1400.
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RESEARCH OVERVIEW
