Anne Simon

BSCI 105  Introduction to Cells and Molecules for majors and non-majors

CBMG 688B  BioEthics

We use small plus-strand RNA viruses to study sequences and structures involved in translation and replication and the switch between these two activities, which are incompatible with each other.  We also study the evolution of 3' translational enhancers and the overlp between translation elements and replication elements.

Precise temporal control is needed for RNA viral genomes to translate sufficient replication-required products before clearing ribosomes and initiating replication. We study the switch between translation and replication using small RNA virus model systems that are translated using a cap-independent mechanism:  Turnip crinkle virus (TCV),  Saguaro cactus virus (SCV), and Pea enation mosaic virus (PEMV).  We recently discovered a new paradigm for translation, where a 3’ translational enhancer in TCV overlaps an internal tRNA-like structure that binds to 60S ribosomal subunits.  We investigate the higher order structure in the region and have found that the tRNA-like structure forms a stable scaffold that allows for simultaneous interactions with external sequences through base pairings on both sides of its large internal symmetrical loop. Binding of TCV RNA-dependent RNA polymerase (RdRp) to the region potentiates a widespread conformational shift with substantial rearrangement of the element required for efficient ribosome binding.  The 3’ end of TCV folds into a compact, highly interactive structure allowing RdRp access to multiple elements including the 3’ end, which causes structural changes that potentiate the shift between translation and replication.  Surprisingly, only one other virus in the same genus as TCV contains a tRNA-like structure in the 3’UTR, and thus we investigate SCV to determine if its Y-shaped structure performs similar functions. 

1.  Zuo, X, Wang, J., Yu, P.,  Eyler, D., Xu, H.,  Starich, M.R., Tiede, D.M., Simon, A.E., Kasprzak, W., Schwieters, C.D., Shapiro, B.A.,  and Wang, Y.-W.  The cap-independent translational enhancer and ribosome binding structure element in 3' UTR of Turnip crinkle virus RNA folds into a tRNA-like shape in solution.  Manuscript submitted.
2. Stupina, V. A., Meskauskas, A., McCormack, J. C., and Simon, A. E.  2009.  Internal ribosome entry in the 5’UTR of Turnip crinkle virus is associated with scanning from the 5’ end.   Manuscript submitted.
3. Yuan, X., Shi, K., Meskauskas, A. and Simon, A.E.  2009.  The 3’ End of Turnip crinkle virus contains a highly interactive structure with a translational enhancer that is disrupted by binding to the RNA-dependent RNA polymerase.  RNA (in press). 
4. Guo, R., Lin, W., Zhang, J., Simon, A. E., and Kushner, D. B.  2009.  Structural plasticity and rapid evolution in a viral RNA revealed by in vivo genetic selection.  J. Virol. 83, 927-939.  
5. Stupina, V. A., Meskauskas, A., McCormack, J. C., Yingling, Y. G., Kasprzak, W., Shapiro, B. A., Dinman, J. D., and Simon, A. E.  2008.  The 3' proximal translational enhancer of Turnip crinkle virus binds to 60S ribosomal subunits.  RNA 14, 2379-2393.  
6. McCormack, J. C., Yuan, X., Yingling, Y. G., Zamora, R. E., Shapiro, B. A., and Simon, A. E.  2008.  Structural domains within the 3' UTR of Turnip crinkle virus.  J. Virol. 82, 8706-8720.  
7. Manfre, A. J., and Simon, A. E.  2008.  Importance of coat protein and RNA silencing in satellite RNA/virus interactions.  Virology 379, 161-167. 
8.  Zhang, J., Zhang, G., Guo, R., Shapiro, B. and Simon, A. E. (2006)  A pseudoknot in a pre-active form of a viral RNA is part of a structural switch activating minus-strand synthesis.  J. Virol 80, 9181-9191.  
9. Zhang, J., Zhang,  G., McCormack, J. and Simon, A. E. (2006).  Evolution of virus-derived sequences for high level replication of a subviral RNA.  Virology 351, 476-488.  
10. Sun, X., and Simon, A. E.  (2006) A cis-replication element functions in both orientations to enhance replication of Turnip crinkle virus.  Virology 352, 39-51.  
11. Zhang, G., Zhang, J., George, A. T., Baumstark, T., and Simon, A. E.  (2006)  Conformational changes involved in initiation of minus-strand synthesis of a virus-associated RNA.  RNA 12, 147-162.  
12. Zhang, J. and Simon, A. E.  2005.  Importance of sequence and structural elements within a viral replication repressor Virology 333, 301-315.  
13. Sun, X., Zhang, G., and Simon, A. E. 2005.  Short internal sequences involved in RNA replication and virion accumulation in a subviral RNA of Turnip crinkle virus. J. Virol. 79, 512-524.  
14. Zhang, J., Stuntz, R. M., and Simon, A. E.  2004. Analysis of a viral replication repressor:  Sequence requirements in the large symmetrical loop. Virology 326,90-102.  
15. McCormack, J. and Simon, A. E. 2004.  Biased hypermutagensis associated with mutations in an untranslated hairpin of an RNA virus.  J. Virol. 78, 7813-7817. 
16. Zhang G, Zhang, J., Simon,  A. E. 2004.  Repression and derepression of minus-strand synthesis in a plus-strand RNA virus replicon.  J. Virol. 78, 7619-7633.

B.A., University of California San Diego

Ph.D., Indiana University, 1982

Postdocs, Indiana University, University of California San Diego