Dr. Eric First's Research Focus

Major Research Interests:
Aminoacylation of tRNA, protein:nucleic acid interactions, enzyme catalysis, nuclear translocation, apoptosis.

Aminoacyl-tRNA synthetases catalyze the covalent attachment of an amino acid to transfer RNA by the following two step reaction:

Enzyme + Amino acid + ATP -> Enzyme·Aminoacyl-AMP + PPi (1)

Enzyme·Aminoacyl-AMP + tRNA ->Enzyme + Aminoacyl-tRNA + AMP (2)

Misaminoacylation of tRNA results in the wrong amino acid being incorporated into the polypeptide chain during protein synthesis. One of the goals of our laboratory is to understand how the aminoacyl-tRNA synthetases in general, and tyrosyl-tRNA synthetase in particular, specifically recognize and aminoacylate their cognate tRNA substrates. A second goal involves the nuclear translocation of aminoacyl-tRNA synthetases. In eukaryotes, a small fraction of the aminoacyl-tRNA synthetases are translocated into the nucleus, where they proofread their cognate tRNAs prior to secretion of the newly synthesized tRNAs into the cytoplasm. Our laboratory is investigating the mechanism that controls the nuclear translocation of human tyrosyl-tRNA synthetase. Finally, aminoacyl-tRNA synthetases play a number of roles that are independent of their role in catalyzing the aminoacylation of tRNA. In particular, the human tyrosyl-tRNA synthetase is secreted into the extracellular media during apoptosis, where it is cleaved to generate two novel cytokines. These tyrosyl-tRNA synthetasederived cytokines are postulated to play a role in attracting macrophages to the site of apoptosis, where they remove the cellular corpses that result from apoptosis. Our laboratory is currently investigating how the secretion of human tyrosyl-tRNA synthetase is regulated during apoptosis. We are using a variety of methods to address the above problems, including protein chemistry, enzyme kinetics, recombinant DNA technology, and cell culture techniques.