Messenger RNA Processing

Mohamed Ghazy
Research Associate
Ph.D. Biochemistry & Molecular Biology, State University of New York, Buffalo
MS, Biochemisty & Molecular Biology, Ain Shams University, Cairo, Egypt
BS Biochemistry, Ain Shams University

Thesis Topic
Mechanism of transcription initiation in the yeast Saccharomyces cerevisiae

Current Research
My current focus is to study the molecular mechanism of mRNA 3’ end processing, its regulation, and its interaction with other processes involved in mRNA synthesis and utilization using the model organism, Saccharomyces cerevisiae; my research focused on the cleavage and polyadenylation factor Pta1which functions in pre-mRNA cleavage, poly(A) addition, transcription termination, snoRNA termination and for the gene looping. Furthermore, different regions of Pta1 interact with the CPF subunits Ssu72, Pti1 and Ysh1 supporting the idea that Pta1 acts as a scaffold to organize CPF. In addition to that I’m working to develop new drug therapies for fungal infections by screening Saccharomyces cerevisiae for small-molecule inhibitors of mRNA 3’ end formation. The screen utilizes an assay in which defects in 3’ end processing lead to production of a reporter required for cell growth (this project is in collaboration with the Broad Institute of Harvard and M.I.T.).

Publications

1. Pardee,T.S., Ghazy, M.A., and Ponticelli, A.S. (2003). Yeast and Human RNA Polymerase II Elongation Complexes: Evidence for Functional Differences and Postinitiation Recruitment of Factors. Eukaryotic Cell. 2: 318-327.
2. Ghazy, M.A., Brodie, S.A., Ammerman, M.L., Ziegler, L.M. and Ponticelli, A.S. (2004). Amino acid substitutions in yeast TFIIF confer upstream shifts in transcription initiation and altered interaction with RNA polymerase II. Mol. Cell. Biol. 24: 10975-85.
3. Majovski, R.C., Khaperskyy, D.A., Ghazy, M.A., and Ponticelli, A.S. (2005). A Functional Role for the Switch 2 Region of Yeast RNAPII in Transcription Start Site Utilization and Abortive Initiation. J. Biol. Chem. 280(41): 34917-23.
4. Saguez C., Schmid M., Olesen J. R., Ghazy, M.A., Poulsen M. B., Nasser T., Moore C., and Jensen T. H. (2008). Nuclear mRNA surveillance in THO/sub2 mutants is triggered by inefficient polyadenylation. Mol. Cell 31(1): 91–103.
5. Ghazy, M.A., He, X., Singh, B.N., Hampsey, M., and Moore C. 2009). The essential N-terminus of the Pta1 scaffold protein is required for snoRNA transcription termination and Ssu72 function but is dispensable for pre-mRNA 3’-end processing. Mol. Cell. Biol. 29 (8): 2296-2307.
6. Krishnamurthy, S., Ghazy, M.A., and Moore, C., and Hampsey, M. (2009). Functional Interaction of the Ess1 Prolyl Isomerase with Components of the RNA Polymerase II Initiation and Termination Machineries. Mol. Cell. Biol. 29 (11): 2925-2934.