Eric M. Phizicky, Ph.D.

Eric M. Phizicky, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, NY 14642

Office: (585) 275-7268
Fax: (585) 271-2683

Research Bio

tRNA Biogenesis, Function and Quality Control



One major lab project focuses on understanding the biology of tRNA. tRNA plays a crucial role in translation, and numerous factors participate in its biogenesis, function, intracellular trafficking, and quality control. In the yeast Saccharomyces cerevisiae, cytoplasmic tRNAs have an average of 13 modifications, and there are a total of 25 chemically distinct modifications, many of which are highly conserved in different organisms, and of unknown function. We previously used a biochemical genomics approach to identify the genes encoding a number of different modification enzymes. We are currently focusing on the assignment of other activities to genes, and on two aspects of the biology of modifications: First, we are investigating the roles of modifications. We recently found evidence that lack of certain modifications can lead to rapid degradation of specific mature tRNAs, suggesting the existence of a quality control pathway that monitors the integrity of tRNA. We are currently working to define the components of this rapid tRNA decay pathway, the mechanism by which tRNAs are targeted for turnover, and the conditions under which this pathway is used. Second, we are defining the mechanisms by which modification enzymes recognize and act on their specific tRNA substrates. Since modifications have crucial roles in the cell, incorrect modification of a tRNA is likely to have catastrophic effects. We recently found that recognition of the tRNAHis anticodon is necessary and sufficient for Thg1 to add a guanine nucleotide to the 5' end of the tRNA, a reaction that is essential in wild type cells for proper translation. We are currently examining other modification enzymes to uncover the different mechanisms by which specificity is attained.

Functional Genomics

A second major lab project focuses on the design, construction and implementation of genomic methods to analyze protein structure and function (in collaboration with Elizabeth Grayhack). To facilitate parallel biochemical analysis of the proteome, we previously constructed two genomic libraries of strains in which nearly every yeast gene is expressed as a tagged fusion protein under regulated control. We are currently using these libraries to define new biochemical activities, and to help define cell circuitry by systematic analysis of genetic suppression caused by overexpression of genes. In addition, in collaboration with investigators at the Hauptman-Woodward Institute, we are developing methodology for high throughput expression and purification of protein complexes from yeast, for structural analysis by x-ray crystallography.

Recent Journal Articles

Showing the 5 most recent journal articles. 59 available »

2014 Aug 12
Zhang X, Walker RC, Phizicky EM, Mathews DH. "Influence of Sequence and Covalent Modifications on Yeast tRNA Dynamics." Journal of chemical theory and computation. 2014 Aug 12; 10(8):3473-3483. Epub 2014 May 28.
2014 Aug 1
Guy MP, Young DL, Payea MJ, Zhang X, Kon Y, Dean KM, Grayhack EJ, Mathews DH, Fields S, Phizicky EM. "Identification of the determinants of tRNA function and susceptibility to rapid tRNA decay by high-throughput in vivo analysis." Genes & development. 2014 Aug 1; 28(15):1721-32.
2012 Oct
Dewe JM, Whipple JM, Chernyakov I, Jaramillo LN, Phizicky EM. "The yeast rapid tRNA decay pathway competes with elongation factor 1A for substrate tRNAs and acts on tRNAs lacking one or more of several modifications." RNA. 2012 Oct; 18(10):1886-96. Epub 2012 Aug 15.
2012 Apr
Grant TD, Snell EH, Luft JR, Quartley E, Corretore S, Wolfley JR, Elizabeth Snell M, Hadd A, Perona JJ, Phizicky EM, Grayhack EJ. "Structural conservation of an ancient tRNA sensor in eukaryotic glutaminyl-tRNA synthetase." Nucleic acids research. 2012 Apr; 40(8):3723-31. Epub 2011 Dec 17.
2011 Jun 1
Whipple JM, Lane EA, Chernyakov I, D'Silva S, Phizicky EM. "The yeast rapid tRNA decay pathway primarily monitors the structural integrity of the acceptor and T-stems of mature tRNA." Genes & development. 2011 Jun 1; 25(11):1173-84.

Current Appointments

Dean's Professorship - Department of Biochemistry and Biophysics (SMD)
Professor - Department of Biochemistry and Biophysics (SMD) - Primary
Professor - Cancer Center
Professor - Department of Pediatrics (SMD)

Education

PhD | Biochemistry | Cornell University1983
BS | Biochemistry | McGill University1976