Blaine Mooers, Ph.D.
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 (*corresponding author, pdb codes from structures determined in my lab or by me): [MyNCBI Bibliography][Google Scholar Bibliography] [Search Pubmed for Mooers-BH]
- Mooers, B. H. M.* (published on-line 2 August 2016) Simplifying and enhancing the use of PyMOL with horizontal scripts. Protein Sci.
- Cruz-Reyes, J., Mooers, B.H.M., Abu-Adas, Z., Kumar, V., & Gulati, S. (published on-line 6 June 2016) DEAH-RHA helicase• Znf cofactor systems in kinetoplastid RNA editing and evolutionarily distant RNA processes. RNA & Disease 3
- Mooers, B. H. M.* (2016) Direct-methods structure determination of a trypanosome RNA-editing substrate fragment with translational pseudosymmetry. Acta Cryst. D72, 477-487. doi: 10.1107/S2059798316001224. 5AD6.
- Kumar, V., Madina, B.R., Gulati, S., Vashishti, A.A., Kanyumbu, C., Pieters, B., Shakir, A., Wohlschlegel, J.A., Read, L.K., Mooers, B.H.M. & Cruz-Reyes, J. (2016) REH2C helicase and GRBC subcomplexes may base pair through mRNA and small guide RNA in kinetoplastid editosomes. J. Biol. Chem. 291,5753-64. doi: 10.1074/jbc.M115.708164
- Gu, X., Mooers, B.H.*, Thomas, L.M., Malone, J., Harris, S.M., and Schroeder, S.J.* (2015) Structures and energetics of four adjacent G·U pairs that stabilize an RNA helix. J. Phys. Chem. B. 119,13252-61. doi: 10.1021/acs.jpcb.5b06970. PMID: 26425937. PDB-code: 4PCO.
- Terzyan, S.S., Burgett, A.W., Heroux, A., Smith, C.A., Mooers B.H., and Hanigan, M.H. (2015) Human Gamma-glutamyl transpeptidase 1: structures of the free enzyme, inhibitor-bound tetrahedral transition states and glutamate bound enzyme reveal novel movement within the active site during catalysis. J Biol Chem. 290,17576-86. doi: 10.1074/jbc.M115.659680. PMID: 26013825.
- Madina, B.R., Kumar, V., Mooers, B.H.M., and Cruz-Reyes*, J. (2015) Native variants of the MRB1 complex exhibit specialized functions in kinetoplastid RNA editing. PLoS One 10(4):e0123441. doi: 10.1371/journal.pone.0123441. PMID: 25928631.
- Mooers, B.H.M.* (2015) RNA Fusions in crystallographic studies of double-stranded RNA from trypanosome RNA editing. Methods in Mol. Biol. 1240, 191-216. doi:10.1007/978-1-4939-1896-6_14. PMID: 25352146.
- Criswell, A. and Mooers, B.H.M.* (2015) Structural studies of a double-stranded RNA trypanosome RNA editing by small-angle X-ray scattering. Methods in Mol. Biol. 1240, 191-216. doi: 10.1007/978-1-4939-1896-6_13. PMID: 25352145.
- Madina, B.R., Kumar, V., Metz, R., Mooers, B.H.M. Bundschuh, R., and Cruz-Reyes, J. (2014). Native mitochondrial RNA-binding complexes in kinetoplastid RNA editing differ in guide RNA composition. RNA 20, 1142-52. doi:10.1261/rna.044495.114. PMID: 24865612.
- Ding, J., Mooers, B.H.M., Zhang, Z., Kale, J., Falcone, D., McNichol, J., Huang, B., Zhang, X.C., Xing, C., Andrews, D.W., and Lin, J. (2014). After embedding in membranes antiapoptotic Bcl-XL protein binds both Bcl-2 homology region 3 and helix 1 of proapoptotic Bax protein to inhibit apoptotic mitochondrial permeabilization. J. Biol. Chem. 289, 11873-96. doi:10.1074/jbc.M114.552562. PMID: 24616095.
- Sheikh, M.O., Schafer, C.M., Powell, J.T., Rodgers, K.K., Mooers, B.H.M., and West, C.M. (2014) Glycosylation of Skp1 affects its conformation and promotes binding to a model F-box protein. Biochemistry 53, 1657-69. doi:10.1021/bi401707y. PMID: 24506136.
- West, M.B., Chen, Y., Wickham, S., Heroux, A., Cahill, K., Hanigan, M.H., and Mooers, B.H.M.* (2013)Novel insights into eukaryotic γ-glutamyl transpeptidase 1 from the crystal structure of the glutamate-bound human enzyme. J. Biol. Chem. 288, 31902-31913. doi:10.1074/jbc.M113.498139. PMID: 24047895. PDB-codes: 4GDX, 4GG2.
- Mooers, B.H.M.* (2013)Structural studies of U-insertion/deletion RNA editing in trypanosomes. In Maas, S. (ed) RNA Editing: Current Research and Future Trends. Caister Academic Press, Norfolk. p. 91-124.
Venkatramani, L., Johnson, E.S., Kolavi, G., Air, G.M., Brouillette W.J.*, Mooers B.H.M.*
(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.
12:7. doi: 10.1186/1472-6807-12-7. PMID: 22559154. PDB-Code: 4DGR.
Mooers, B.H.M.* & Singh, A. (
2011) The crystal structure of an oligo(U):pre-mRNA duplex from a trypanosome RNA editing substrate. RNA
17, 1870-83. doi: 10.1261/rna.2880311. PMID; 21878548. PDB-Code: 3ND3, 3ND4.
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. PDB-Codes: 3C7Y
, 3C81, 3C82
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. doi: 10.1002/pro.93. PMID:19384984. PDB-Codes: 3F8V, 3F9L, 3FA0, 3FAD
Mooers, B.H.M.* (2008) Crystallographic studies of DNA and RNA. Methods 47, 168-176. doi: 10.1016/j.ymeth.2008.09.006. PMID: 18848992.
& 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.doi:10.1107/S0907444905037212
. PMID: 16421448. PDB-Codes: 2ANX, 2ANV
Mooers,B.H.M., 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.
- doi: 10.1073/pnas.0505873102. PMID: 16269545.
& 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. doi:10.1107/S0907444904017020
. PMID: 15388918. PDB-Codes: 1SWZ
, and 1SWY
Sagermann, M., Gay, L., Mooers, B.H.M., & 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.
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. PDB-Codes: 1PQM