个人简介

PhD | Biochemistry | Cornell University 1983 BS | Biochemistry | McGill University 1976

研究领域

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.

近期论文

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2015 Feb Han L, Kon Y, Phizicky EM. "Functional importance of ?38 and ?39 in distinct tRNAs, amplified for tRNAGln(UUG) by unexpected temperature sensitivity of the s2U modification in yeast." RNA. 2015 Feb; 21(2):188-201. Epub 2014 Dec 12. 2015 Jan Guy MP, Phizicky EM. "Conservation of an intricate circuit for crucial modifications of the tRNAPhe anticodon loop in eukaryotes." RNA. 2015 Jan; 21(1):61-74. Epub 2014 Nov 17. 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. Guy MP, Phizicky EM. "Two-subunit enzymes involved in eukaryotic post-transcriptional tRNA modification." RNA biology. 2014 11(12):1608-18.