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Associate Professor; Ph.D., Moscow State University; Office Phone: (216) 687-2516 Lab Phone: (216) 523-7259 e-mail: a.komar@csuohio.edu |
Our research is concerned with protein synthesis and translational control of gene expression in eukaryotic cells. Recent studies have pointed to the key role of translational control in regulating gene expression during development, differentiation, cell cycle progression, cell growth, apoptosis, and stress. Regulation of translation is mainly exerted at the initiation step of protein synthesis, thus allowing rapid modification of the overall rate of translation as well as post-transcriptional regulation of gene expression due to changes in the relative selection of different mRNA species utilizing different mechanisms of translation initiation.
Assembly of the 80 S ribosome at a start codon within the majority of eukaryotic mRNAs involves recruitment of the 40 S ribosome (and associated initiation factors) to the mRNA 5'-end followed by ribosome scanning (in search of the initiation codon). However, it was shown that some viral and eukaryotic cellular mRNAs can be translated via internal initiation, a process that is generally independent of the recognition of the 5'-mRNA end and involves direct recruitment of the 40 S ribosome to the vicinity of the initiation codon (directed by internal ribosome entry site (IRES) elements).
We have recently discovered an IRES element in the yeast Saccharomyces cerevisiae URE2 mRNA. Unlike many other IRES elements URE2 IRES is located in the open reading frame of the URE2 gene and triggers the synthesis of an amino-terminally truncated form of the protein (amino acids 94-354). Ure2p is a regulator of nitrogen catabolism in yeast cells and is a protein with prion like properties. Its N-terminal domain (amino acids 1-93) is necessary and sufficient for prion propagation, whereas its C-terminal domain is responsible for nitrogen regulation. We have shown that internal initiation driven by URE2 IRES element affects [URE3]-prion propagation in yeast cells.
We are interested in the mechanism of URE2 IRES function and factors that affect its activity. Saccharomyces cerevisiae offers unique possibility to combine the power of yeast genetics with biochemical approaches to decipher the mechanism of internal initiation.
Our research is not confined only to the mechanisms of protein synthesis we are also interested in the protein structure/function relationships relevant to the design of the novel protein drugs.
Komar, A.A., Kommer, A., Krasheninnikov, I.A. and Spirin, A.S. (1997) Cotranslational folding of globin. J. Biol. Chem., 272, 10646-10651.
Komar, A.A., Guillemet, E., Reiss, C. and Cullin, C. (1998) Enhanced expression of the yeast Ure2 protein in Escherichia coli: the effect of synonymous codon substitutions at a selected place in the gene. Biol. Chem., 379, 1295-1300.
Thual, C., Komar, A.A., Bousset, L., Fernandez-Bellot, E., Cullin, C. and Melki, R (1999) Structural characterization of Saccharomyces cerevisiae prion-like protein Ure2. J. Biol. Chem., 274, 13666-13614.
Thual, C., Bousset, L., Komar, A.A., Walter, S., Buchner, J., Cullin, C. and Melki, R. (2001) Stability, folding, dimerization and assembly properties of the yeast prion Ure2p. Biochemistry, 40, 1764-1773.
Zoll, W.L., Horton, L.E., Komar, A.A., Hensold, J.O. and Merrick, W.C. (2002) Characterization of mammalian eIF2A and identification of the yeast homolog J. Biol. Chem., 277, 37079-37087.
Rogers, G.W. Jr., Komar, A.A. and Merrick, W.C. (2002) eIF4A: The Godfather of the DEAD-box Helicases. In Progress in Nucleic Acid Research and Molecular Biology. (K. Moldave, ed.) Academic Press, San Diego, p. 307-331.
Yang, H-S., Jansen, A.P., Komar, A.A., Zheng, X., Merrick, W.C., Costes, S., Lockett, S.J., Sonenberg, N. and Colburn, N.H. (2003) The transformation suppressor Pdcd4 is a novel eIF4A binding protein that inhibits translation. Mol. Cell. Biol., 23, 26-37.
Komar, A.A., Lesnik, T., Cullin, C., Merrick, W.C., Trachsel, H. and Altman, M. (2003) Internal initiation drives the synthesis of Ure2 protein lacking the prion domain and affects [URE3] propagation in yeast cells. EMBO J., 22, 1199-1209.
Yaman, I., Fernandez, J., Liu, H., Caprara, M., Komar, A.A., Koromilas, A., Zhou, L., Snider, M., Scheuner, D., Kaufman, R.J. and Hatzoglou M. (2003) The zipper model of translational control: a small upstream ORF is the switch that controls structural remodeling of an mRNA leader. Cell, 113, 519-531.
Merrick, W.C. and Komar, A.A. (2004) Eukaryotic protein biosynthesis: The elongation cycle. In Encyclopedia of Biological Chemistry (Lennarz W.J. and Lane M. D., eds), Academic Press/Elsevier Science, Elsevier, Oxford, Vol. 4, 224-230.
Fernandez, J., Yaman, I., Huang, C., Liu, H., Lopez, A.B., Komar, A.A., Caprara, M., Merrick, W.C. Snider, M., Kaufman, R.J., Lamers, W.H. and Hatzoglou, M. (2005) Ribosome stalling regulates IRES-mediated translation in eukaryotes, a parallel to prokaryotic attenuation. Mol. Cell. 17, 405-416.
Komar, A.A., Gross, S., Barth-Baus, D., Strachan, R., Hensold, J.O., Kinzy, T. and Merrick, W.C. (2005) Novel characteristics of the biological properties of the yeast Saccharomyces cerevisae initiation factor eIF2A. J. Biol. Chem. 280, 15601-15611.
Komar, A.A. and Hatzoglou, M. (2005) Internal Ribosome Entry Sites in cellular mRNAs: Mystery of their existence. J. Biol. Chem. 280, 23425-23428.
Copyright © 2005
Department of
Biological, Geological, and Environmental Sciences
College of Science,
Cleveland State University
All rights reserved.
Update: 26 September, 2005