Dr. Robert E. Rhoads' Research Focus

Major Research Interests:
Protein synthesis in eukaryotic cells; viral pathogenesis involving translation; messenger RNA structure and function; regulation of cell growth.

Our laboratory studies the mechanism and regulation of protein synthesis in eukaryotic cells, especially as it is affected by growth factors, oncogenes and viruses. The process by which mRNA is recruited to the ribosome involves recognition of the cap by initiation factor eIF4E, unwinding of secondary structure in the 5'-untranslated region by the helicase eIF4A, and binding of mRNA to the 40S subunit by a linking protein called eIF4G. Recently, mRNA recruitment was also shown to involve recognition of the poly(A) tract by poly(A)-binding protein. We are investigating the structure and function of these initiation factors using the tools of protein chemistry, recombinant DNA technology, and in vivo expression. We are also working out the signal transduction pathways that lead from polypeptide hormone receptors on the cell surface to the protein synthesis machinery. We find that the rate of protein synthesis has a profound effect on overall growth control of cells: overexpression of eIF4E and eIF4G using DNA vectors causes cells to become malignantly transformed, whereas underexpression of eIF4E using antisense RNA technology causes malignant cells to revert to a more normal phenotype. Specific projects include the phosphorylation of eIF4E, mechanism of the role of initiation factors in Xenopus maturation, the structure and function of eIF4G isoforms in mammalian cells, the biological role and structural basis for cap recognition by various eIF4E isoforms in the nematode C. elegans, and the relationship between eIF4G and the shut-off of host protein synthesis that occurs during picornavirus infection.