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Biology

 

My Teaching

 

Dr. William Tapprich

Professor and Chair
Ph.D. University of Montana, 1986
Prof. Biochemistry, (Courtesy) UNMC

 

Office: Allwine Hall 211D
Lab: Allwine Hall 232
Office phone:(402) 554-3380"
Lab phone (402) 554-2948
Dept. Fax (402) 554-3532
wtapprich@mail.unomaha.edu

 

Teaching Fields:

  • Molecular Biology
  • Virology
  • Nucleic Acids Biochemistry
  • Protein Structure

Research Interests:

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)
Many of the approaches that we use for determining the structure of rRNA are also applicable to viral RNA. We have initiated studies to learn the structure of the internal ribosome entry site (IRES) RNA found in picornaviruses and flaviviruses (Figure 2 and Figure 3). This work is significant because virulence is determined by IRES structure. In our initial studies we have used chemical modification and primer extension to deduce the secondary structure of the IRES elements in coxsackievirus B3 and bovine diarrhea virus. This analysis has been completed for virulent wild type viruses and for attenuated mutant viruses. We have shown localized structural changes in the IRES RNA that correlate with virulence. Theses shifts in structure occur in regions of the IRES known to be important for the binding of key cellular proteins. The results show that viral replication and viral virulence is critically dependent on discrete structures in the RNA. Further characterization of these structures will lead to strategies to develop antiviral compounds and vaccines.

Figure 2. Crystal structure of a picornavirus virion

Figure 3. Secondary structure model for the IRES element of coxsackievirus B3
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Selected Publications:

  1. 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.
  2. 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
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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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Recent Thesis Titles:

  • Missak, Johanna M. 2005. Structural Analysis of the 5’ Nontranslated Region on the Genomic RNA of Virulent and Nonvirulent Strains of the Coxsackievirus B3.
  • Bailey, Jennifer M. 2004. Structure of 5'Nontranslated Region RNA in Virulent and Nonvirulent Coxsackievirus B3 Genomes.
  • Martinsen, Angela. 2003. Molecular Analysis of Structural Alterations of E. coli 16S rRNA Induced by IF3.
  • Park, John M. 2001. Molecular Detail of the Binding Interaction Between IF3 and 16S rRNA.
  • Ihrig, Timothy G. 2000. Probing the Structure of the 5' NTR of Coxsackievirus B3 RNA.
  • Munger, Corey M. 2000. Analysis of a Potential Base Pair Between 1782U and 2586U in Eschericia coli 23S Ribosomal RNA.
  • Carden, Bruce M. 1998. Analysis of Potential Base-Pairs Between 16S and 23S Ribosomal RNA in Eschericia coli.
  • Yu, Ni 1998. Development of Ovarian Follicles in situ .
  • Brown, Kirk M. 1997. Exploring a Lone Pair Interaction in Escherichia coli 16S Ribosomal RNA Using Site-Directed Mutagenesis.
  • Loyd, Gregory R. 1996. Probing the Extreme 3' End of 16S Ribosomal RNA from Escherichia coli.
  • Bellah, Susan P. 1995. Effects of 5-Fluorouracil on Escherichia coli Ribosomes.
  • Staplin, William R. 1995. Analysis of Subunit Association using Mutations at Position 790 of Escherichia coli rRNA.

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Other Responsibilities: Biotechnology Advisor