It has been shown that modification levels of transfer ribonucleic acids (tRNAs) in malignant tumors varies substantially to that of normally growing cells. Inhibition of translocation elicits slow growth and lethal phenotypes while an acceleration of this process could cause miscoding. The molecular interactions between the ribosome and the tRNAs essential to this process are not fully understood. The focus of my research has been to identify interactions between the ribosome and the tRNAs important for translocation. A hallmark of aggressive malignant tumor growth is the increase in cell proliferation, which requires an overall increase in the translational machinery responsible for protein biosynthesis. Protein synthesis is one of the fundamental steps of gene expression and understanding how cells regulate gene expression normally will provide a better understanding of cancer at a molecular level. The ability to synthesize proteins in a rapid and highly accurate fashion is critical to cell growth. In eukaryotes it has been demonstrated that enzymes known to modify tRNAs have been found at extreme levels in several types of cancer cells, i.e. colon cancer cells, leukemic cells and pancreatic cancer cells. These enzymes or subsequently modified tRNAs may represent a novel target for the development of therapeutic agents once their role in the translational machinery has been characterized.

PUBLICATIONS (resulting from this training)

Feinberg JS, Joseph S. (2001) Identification of molecular interactions between P site tRNA and the ribosome essential for translocation. Proc Natl Acad Sci USA 98:11120-11125.

Studer SM, Feinberg JS, Joseph S. (2003) Rapid kinetic analysis of EF-G-dependent mRNA translocation in the ribosome. J Mol Biol. 327: 369 381.

Feinberg JS, Joseph S. (2006) Ribose 2'-hydroxyl groups in the 5' strand of the acceptor arm of P-site tRNA are not essential for EF-G catalyzed translocation. RNA. 12:580-8.

Feinberg JS, Joseph S. (2006) A conserved base-pair between tRNA and 23 S rRNA in the peptidyl transferase center is important for peptide release. J Mol Biol. 2006 364:1010-20.