Our Science – Dhar Website

Ravi Dhar, Ph.D.

Basic Research Laboratory Head, Yeast Signaling Section Senior Investigator Building 37, Room 6138B NCI-Bethesda 9000 Rockville Pike Bethesda, MD 20892 Phone:   301-496-0990 Fax:   301-496-4951 E-Mail:   dharr@mail.nih.gov

Biography

Dr. Dhar obtained his Ph.D. from Calcutta University, India, and did his postdoctoral work at Yale University with Dr. Sherman Weissman. His major research interest has been the study of gene structure and regulation of DNA and RNA tumor viruses. More recently, he has been using fission yeast as a model system to study the mechanism of nuclear cytoplasmic trafficking.

Research

Nucleocytoplasmic Trafficking in Fission Yeast

The research focus of the laboratory is to understand the mechanism of nucleocytoplasmic trafficking through the nuclear pore. We have used fission yeast Schizosaccharomyces pombei as a model genetic organism and have concentrated on the export of mRNA from the nucleus. We see this process as a three-fold problem: (1) identifying the components involved in mRNA export; (2) defining genetic and physical interactions among components; and (3) elucidating the biochemical function of these proteins.

The prevailing model of mRNA export is one in which mature mRNA binds to a set of proteins of which one or more carry a nuclear export signal (NES). This signal binds to a receptor which then directs the transport of the mRNP through interaction with the transport machinery within the pore. We have used as a starting point for this study the temperature sensitive mutants of rae1 gene that rapidly accumulate poly(A)RNA in the nucleus upon shift to restrictive temperature. The rae1 protein (Rae1p) is a conserved WD repeat protein and associates with the nuclear pore. We have identified several genes that genetically interact with rae1: two genes encoding nucleosporins, npp106 and nup184, and a gene, mex 67, that encodes a nuclear pore-associated protein. Moreover, mex67 genetically interacts with npp106 and nup184. Each of these genes in turn affects the export of mRNA. Moreover, it appears that Rae1p and Mex67p likely function in parallel mRNA export reactions. In contrast to S. cerevisiae, Mex67p is not essential in S. pombe whereas Rae1p is essential. It has been suggested that Mex67p functions in nuclear export of mRNA by directly associating with it and directing its export out of the nucleus. We have identified a novel domain within Mex67p that functions in mRNA export without direct interaction with mRNA. This domain can shuttle between the nucleus and the cytoplasm using novel import-export pathways. We are currently in the process of identifying its interacting partners and receptors that direct its nuclear import and export. In addition, our current work focuses on identifying components of the Rae1p-dependent mRNA export machinery and linking them with components of the Mex67p-dependent mRNA export pathways.

This page was last updated on 6/11/2008.