Coronavirus Replication
In this collaborative project with JL Leibowitz's group at Texas A&M, we are using the tools of biophysical chemistry and NMR spectroscopy to understand the structure and biological function of the very "tips" of the coronavirus genome, the 5' and 3' untranslated regions (UTRs) that direct the replication and propagation of SARS-CoV and closely related group 2 CoVs. We anticipate using mass spectrometry-based fingerprinting methods to identity cellular or virally encoded proteins that interact with specific RNA targets and NMR spectroscopy to solve their structures.
Coronavirus Replication


Solution structure of mouse hepatitis virus (MHV) nsp3a and determinants of the interaction with MHV nucleocapsid (N) protein.
Keane, S. C. & GIEDROC, D. P. (2013)
J. Virol. 87, 3502-3515
View: PubMed

(1)H, (13)C, (15)N resonance assignments of murine hepatitis virus nonstructural protein 3a.
Keane, S. C. & GIEDROC, D. P. (2012)
Biomol. NMR Assign., published online November 8, 2012
View: PubMed

Functional transcriptional regulatory sequence (TRS) RNA binding and helix destabilizing determinants of the murine hepatitis virus (MHV) nucleocapsid (N) protein.
Keane, S. C., Liu, P., Leibowitz, J. L. & GIEDROC, D. P. (2012)
J. Biol. Chem. 287, 7063-7073.
View: PubMed

A conserved RNA pseudoknot in a putative molecular switch domain of the 3'-untranslated region of coronaviruses is only marginally stable.
Stammler, S. N., Cao, S., Chen, S. J., & GIEDROC, D. P. (2011)
RNA 17, 1747-1759.
View: PubMed

Mouse hepatitis virus stem-loop 4 functions as a spacer element required to drive subgenomic RNA synthesis.
Yang, D., Liu, P., GIEDROC, D. P., & Leibowitz, J.
J. Virol. 85, 9199-9209.
View: PubMed

The solution structure of coronaviral stem-loop 2 (SL2) reveals a canonical CUYG tetraloop fold.
Lee, C. W., Li, L.,& GIEDROC, D. P. (2011)
FEBS Lett. 585, 1049-1053.
View: PubMed

Mouse hepatitis virus stem-loop 2 adopts an uYNMG(U)a-like tetraloop structure that is highly functionally tolerant of base substitutions.
Lui, P., Li, L., Keane, S. C., Yang, D., Leibowitz, J. L. & GIEDROC, D. P. (2009)
J. Virol. 83, 12084-12093.
View: PubMed

Coronavirus N protein N-terminal domain (NTD) specifically binds the transcriptional regulatory sequence (TRS) and melts TRS-cTRS RNA duplexes.
Grossoehme, N. E., Li, L., Keane, S. C., Liu, P., Dann, C. E., III, Leibowitz, J. L., & GIEDROC, D. P.  (2009)
J. Mol. Biol. 394, 544-557.
View: PubMed

Structural lability in stem-loop 1 drives a 5' UTR-3' UTR interaction in coronavirus replication.
Li, L., Kang, H., Liu, P., Makkinje, N., Williamson, S. T., Leibowitz, J. L., and Giedroc, D. P. (2008)
J. Mol. Biol.377,790-803.
View: PubMed

A U-turn motif-containing stem-loop in the coronavirus 5' untranslated region (UTR) plays a functional role in replication.
Liu, P., Li, L., Millership, J. J., Leibowitz, J. L., & Giedroc, D. P. (2007)
RNA 13, 763-780.
View: PubMed

Cis-acting stem-loops in the 5' untranslated region of the severe acute respiratory syndrome coronavirus can substitute for their MHV counterparts.
Kang, H., Feng, M., Schroeder, M. E., Giedroc, D. P., & Leibowitz, J. L. (2006)
J. Virol. 80, 10600-10614.
View: PubMed