The overall goal of our research is to understand the structure and function of RNA molecules. Most of our work has focused on ribosomal RNA (rRNA), characterizing the role of the RNA in protein synthesis (Thompson et al 2001, Vila et al 1994). We have recently embarked on a new area of investigation studying the structure and function of viral RNA molecules.
Our current projects on rRNA seek to understand the dynamic nature of the RNA during protein synthesis. One of our projects investigates the interaction of initiation factor 3 (IF3) on the small ribosomal subunit. Using chemical probes, we have pinpointed nucleotides that shift conformation during IF3 binding. Mutations in rRNA that preclude these shifts are deleterious to IF3 interaction and cell viability. A second set of projects uses mutagenesis of rRNA to investigate the importance of tertiary interactions in rRNA. This analysis has revealed a number of critically important lone pair interactions in both small subunit and large subunit rRNA. Over the last several years, crystallographic analysis has generated atomic resolution models of the ribosome and rRNA (Figure 1). This has greatly enhanced our understanding of rRNA and protein synthesis. By focusing on rRNA dynamics we hope to contribute elements of movement to the current rRNA models.
Figure1 Crystal structure of the small ribosomal subunit. From:Brian T. Wimberly, Ditlev E. Broderson, William M. Clemons Jr, Robert J. Morgan-Warren, Andrew P. Carter, Clemens Vonrhein, Thomas Hartsch and V. Ramakrishnan. Nature 407, 327 - 339 (2000)
- Bailey, J. M. and Tapprich, W. E. (2007) “Structure of the 5’ Nontranslated Region of the Coxsackievirus B3 Genome: Chemical Modification and Comparative Sequence Analysis” J. Virol. 81:650-668.
- Tracy, S, Chapman, N. M., Drescher, K. M. and Tapprich, W. (2006) “Evolution of Virulence in Picornaviruses.” Curr. Top. Micro. and Immonol. 299:193-210
- Kim, K-S, Tracy S, Tapprich, W.E., Bailey, J., Lee, C-G, Kim K, Barry, WH and Chapman, NM (2005) “5’ Terminal Deletions Occur in Coxsackievirus B3 During Replication in Murine Hearts and Cardiac Myocyte Cultures and Correlate with Encapsidation of Negative Strand Viral DNA.” J. Virol. 79:7024-7041.
- Xiong W., Tapprich W.E. and Cox G.S. (2002) “Mechanism of Gonadotropin Gene Expression: Identification of a Novel Negative Regulatory Element at the Transcription Start Site of the Glycoprotein Hormone alpha Subunit Gene”.J Biol Chem 277(43):40235-46.
- Thompson, J., Tapprich, W.E., Munger, C. and Dahlberg, A.E. (2001) “Staphlococcus aureus domain V functions in E. coli ribosomes provided a conserved interaction with domain IV is restored.” RNA 8:1076-83.
- Vila, A., Viril-Farley, J. and Tapprich, W. E. (1994) "Pseudoknot in the Central Domain of Small Subunit Ribosomal RNA is Essential for Translation." Proc. Natl. Acad. Sci. USA 91: 11148-11152.
- Lodmell, J. S., Tapprich, W. E. and Hill, W. E. (1993) "Evidence for a Conformational Change in the Exit site of the Escherichia coli Ribosome upon tRNA Binding." Biochemistry 32: 4067-4072.
- Melancon, P., Tapprich, W. E. and Brakier-Gingras, L. (1992) "Single-Base Mutations at Position 2661 of Eschericia coli 23S rRNA Increase Efficiency of Translational Proofreading." J. Bacteriology, 174: 7896-7901.Hill, W. E., Tassanakajohn, A. and Tapprich, W. E. (1990) "Interaction of tRNA with domain II of 23S rRNA." Biochim, Biophys. ACTA, 1050: 45-50.
- Tapprich, W. E. and Dahlberg, A. E. (1990). "A Single Base Mutation at Position 2661 in Escherichia coli 23S Ribosomal RNA Affects the Binding of Ternary Complex to the Ribosome." EMBO J., 9: 2649-2655.
- Tapprich, W. E., Göringer, H. U., De Stasio, E. A., Prescott, C. and Dahlberg, A. E. (1990) "Studies of Ribosome Function by Mutagenesis of Escerichia coli rRNA" In: The Ribosome: Structure, Function and Evolution, W. Hill, A. Dahlberg, R. A. Garrett, P. B. Moore, D. Schlessinger, J. R. Warner eds. ASM Press, Washington DC.
- Hill, W. E., Gluick, T., Marconi, R. T., Merryman, C., Tassanakajohn, A., Weller, J. and Tapprich, W. E. (1990) "Probing Ribosome Structure and Function by using Short, Complementary DNA Oligonucleotides" In: The Ribosome: Structure, Function and Evolution, W. Hill, A. Dahlberg, R. A. Garrett, P. B. Moore, D. Schlessinger, J. R. Warner eds. ASM Press, Washington DC.
- Tapprich, W. E., Göringer, H. U., De Stasio, E. A. and Dahlberg, A. E. (1990) "Site-Directed Mutagenesis of Ribosomal RNA." In: Ribosomes a Practical Approach, G. Spedding ed. IRL Press, Oxford, UK.
- Tapprich, W. E., Goss, D. J. and Dahlberg, A. E. (1989) "A Mutation at Position 791 in Escherichia coli 16S Ribosomal RNA Affects Processes Involved in the Initiation of Protein Synthesis." Proc. Natl. Acad. Sci. USA 86: 4927-4931.
- De Stasio, E. A., Göringer, H. U., Tapprich, W. E. and Dahlberg A. E. (1988) "Probing Ribosomal Function Through Mutagenesis of Ribosomal RNA" In: Genetics of Translation. Tuite, M. F., Picard, M. and Bolotin-Fukuhara eds. Springer-Verlag, Berlin.
- Hill, W. E., Tapprich, W. E., Camp, D. G. and Tassanakajohn, A. (1988) "Probing Ribosomal Structure and Function using Complementary Oligonucleotides." Meth. Enz. 164, 605-625.
- Hill, W. E., Tapprich, W. E. and Tassanakajohn, A. (1986) "Probing Ribosomal Structure and Function." In: Structure, Function and Genetics of Ribosomes. Hardesty, B. etc eds. Springer-Verlag, Berlin.
- Tapprich, W. E. and Hill W. E. (1986) "The Involvement of Bases 787-795 of Escherichia coli 16S Ribosomal RNA in Ribosomal Subunit Association." Proc. Natl. Acad. Sci. USA 83, 556-560.
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