Organizing Committee Member
Nayef Jarrous
Chair in Human Biochemistry
The Hebrew University-Hadassah Medical School
Israel
Biography
Prof. Nayef Jarrous is Jacob Ziskind Chair in Human Biochemistry, at Department of Microbiology and Molecular Genetics, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel. He has completed his Doctoral degree (PhD) in Molecular Biology from Hebrew University, Jerusalem, Israel in 1996. His research interest includes Biochemical studies of catalytic ribonucleoprotein complexes of human RNase P, Elucidation of the molecular mechanisms by which ribonucleoprotein complexes of RNase P controls gene transcription by RNA polymerase I and III and RNase P, DNA damage, aging and cancer. He was invited speaker at international scientific meetings and conferences.
Research Area
We study the biosynthesis of transfer RNA (tRNA), which serves as the adaptor in transferring of the genetic information from mRNA to protein in the cell. Specifically, we investigate transcription of human tRNA genes by RNA polymerase III (Pol III) and subsequent processing and splicing of newly transcribed precursor tRNAs. Processing of precursor tRNA requires ribonuclease P (RNase P), an essential ribonucleoprotein enzyme. Biochemical purification analyses of nuclear RNase P from human cells have revealed that this large ribonucleoprotein complex has an RNA subunit, termed H1 RNA, and ten distinct protein subunits. We have characterized many of these protein subunits and reconstituted the endonucleolytic activity of RNase P in processing of precursor tRNA in vitro by the use of H1 RNA and recombinant protein subunits. The roles of H1 RNA and its protein subunits in RNA-based catalysis and substrate recognition are being further investigated. More recent discoveries from our laboratory reveal that a form of human RNase P is required for transcription of small noncoding RNA genes by Pol III. Pol III transcribes an expanding number of genes, including tRNA, 5S rRNA, SRP RNA, 7SK RNA and U6 snRNA genes. The noncoding RNA transcripts of these genes participate in fundamental biological processes, such as transcription, mRNA splicing and translation. RNase P associates with Pol III in initiation complexes, which are controlled by proto-oncogenes and tumor suppressor genes, and binds to chromatin of tRNA and 5S rRNA genes in a cell cycle-dependent manner. Ongoing research focuses on the elucidation of the molecular mechanisms by which RNase P exerts its role on Pol III transcription and how transcription and processing of precursor tRNA are coordinated in confined nuclear compartments. An emerging area of research concerns the molecular designing and use of RNase P for the inactivation of expression of human genes associated with aging and cancer. This research led to the discovery that RNase P and Pol III respond to cessation of replication progression and DNA damage that lead to mitotic catastrophe and cell death of cancer cells. Moreover, through collaborative work, we have shown that a form of human RNase P is involved in DNA repair of double stranded breaks (DSBs) via the homology directed repair pathway.