Ou Medicine

Blaine Mooers, Ph.D.

Assistant Professor Biochemistry & Molecular Biology Ph.D., Oregon State, 1997 Phone: (405) 271-8300 Fax:     (405) 271-3910 E-mail: blaine-mooers@ouhsc.edu    Mailing Address:  975 N.E. 10th, BRC468  Oklahoma City, OK  73104 Mooers Lab Staff Crystallography & Molecular Graphics Software Links Small Angle X-ray Scattering Links Oklahoma COBRE in Structural Biology Stephenson Cancer Center at OU OU Supercomputing Center for Education and Research OUHSC Macromolecular Crystallography Lab Oklahoma Structural Biology Nexus

Structural biology of messenger RNA editing in the mitochondria of trypanosomes using X-ray crystallography and other physical techniques. Uridine (U) insertion/deletion editing in trypanosomes is an extensive post-transcriptional process that corrects the coding sequence of most mitochondrial mRNAs.  This editing is required for the subsequent expression of several mitochondrial proteins.  The number of Us that are inserted far exceeds that number that are deleted; there is a net increase in the number of codons after editing.  An enzyme cascade does the editing in the mitochondrion.  The editing reactions are directed by a number of different guide RNAs.  Each guide RNA has the sequence complement of a fragment of the final edited mRNA sequence. Consequently, much of the genetic information for the final RNA transcript comes from both its corresponding gene and the genes for the set of guide RNAs that direct its editing.  In other words, the genetic information flows from DNA to RNA along multiple parallel pathways.  This is an interesting variation of the central paradigm of molecular biology that information flows along one pathway from DNA-->RNA-->protein.  The evolutionary basis for such a complex and expensive system of information flow is still unclear. 

Our goal is to obtain a rigorous description of the structural biology of this type of RNA editing to improve our understanding of its evolutionary basis, clarify the relationship between this type of RNA editing and other types of RNA editing, and to provide a structural basis of the design of better drugs to fight infections with trypanosomes which threaten 600 million people worldwide. 

Selected Publications:                          [Search Pubmed] 

• Mooers BHM. RNA Editing: Current Research and Future Trends. Maas S editor. Norfolk, England: Caister Academic Press; 2013. Chapter 5, Structural studies of U-insertion/deletion RNA editing in trypanosomes; p.91-124. 236p
• Venkatramani L, Johnson ES, Kolavi G, Air GM, Brouillette WJ, Mooers BH. (2012) Crystal structure of a new benzoic acid inhibitor of influenza neuramidase bound with a new tilt induced by overpacking sub-site C6.  BMC Struct Biol. May 6;12(1):7. [Epub ahead of print]
• Mooers, B.H.* & Singh, A. (2011) The crystal structure of an oligo(U):pre-mRNA duplex from a trypanosome RNA editing substrate. RNA 17, 1870-83. *Corresponding author.
• Mooers, B.H., Baase, W.A., Wray, J.W., & Matthews, B.W.  (2009)  Contributions of all 20 amino acids at site 96 to the stability and structure of T4 lysozyme.  Protein Sci. 18, 871-880. 
• Mooers, B.H., Tronrud, E.D., & Matthews, B.W. (2009)  Evaluation at atomic resolution of the role of strain in destabilizing the temperature-sensitive T4 lysozyme mutant Arg 96 --> His. Protein Sci. 18, 863-870.
• Mooers, B. H. (2008)  Crystallographic studies of DNA and RNA. Methods 47, 168-176. 
• Mooers, B. H.*  & Matthews, B. W.  (2006)  Extension to 2268 atoms of direct methods in the ab initio determination of the unknown structure of bacteriophage P22 lysozyme. Acta Cryst. D 62, 165-76.  *Corresponding author.
• Mooers, B. H., Logue, J. S. & Berglund, J. A. (2005)  The structural basis of myotonic dystrophy from the crystal structure of CUG repeats. Proc. Nat. Acad. Sci., USA 102, 16626-16631. 
• Mooers, B. H. & Matthews, B. W. (2004) Use of an ion binding site to by-pass the 1000 atom limit to ab initio structure determination by direct methods. Acta Cryst. D 60, 1726-1737.
• Sagermann, M. Gay, L., Mooers, B. H., & Matthews, B. W.  (2004)  Relocation or duplication of the helix A sequence of T4 lysozyme causes only modest changes in structure but can increase or decrease the rate of folding.Biochemistry 33, 1296-301.
• Mooers, B. H., Datta, D., Zollars, E., Mayo, S. L., & Matthews, B. W. (2003) Repacking the core of T4 lysozyme by automated design. J. Mol. Biol.  332, 741-756.