Rice University
BioSciences at Rice

Edward Nikonowicz

Associate Professor of BioSciences

Our laboratory focuses on understanding structure-function relationships in nucleic acid systems. In addition to NMR spectroscopy, we use biochemical and other biophysical methods (SAXS, single molecule FRET, x-ray crystallography) to investigate the kinetic, motional, and structural properties of the component molecules.

 The data obtained from these methods complement physiological and genetic information. One focus of the lab centers on post-transcriptional modification of tRNA and the contributions of modifications to tRNA-mediated gene expression through T-box riboswitch mechanism. The bases of tRNA molecules are modified in all cells. Modification, especially within the anti-codon loop, has been linked to translational fidelity and efficiency and regulation in prokaryotes. We are examining structural properties and the kinetic parameters of T-box riboswitch-tRNA binding to develop mechanistic models. Modifications throught tRNA affect the molecule's structure and stability. We are elucidating the roles of various tRNA modifications on the efficiency of riboswitch function in the cell and on the kintics of riboswitch-tRNA binding. These studies also will extend our understanding of the contributions of tRNA modification to Gram positive bacterial cell physiology and fitness. 

 Non-coding RNAs (nc-RNA), including rRNAs, riboswitches, and pre-microRNAs, often have an architecture containing a variety of non-canonical features that are key for the molecules' structures and function, therefore, the detailed structure provides an important backdrop to interpret functional and mechanistic studies. Small molecules that bind to specific RNA structure motifs can become powerful tools for probing RNA conformation and folding and to facilitate studies of specific RNA activities in vitro and in vivo. We are using NMR spectroscopy to define the breadth of conformational space accessed by a set of frequently occurring non-canonical RNA motifs. A computational workflow, that integrates the NMR-defined structure information and in silico screening of virtual chemical libraries is being used to identify chemical compounds that selectively bind to these non-canonical motifs. The interactions of these small molecules with RNAs are being characterized using biophysical and high-resolution structure methods including NMR spectroscopy and X-ray crystallography. 

 Another system involves the interaction of primary ribosomal proteins with their RNA targets and provides the opportunity to not only explore the specificity of RNA-ligand interactions, but also to examine the co-folding of protein and RNA molecules and maturation of the 30S (prokaryotic) and 40S (eukaryotic) ribosomal subunit. The primary RNA binding site for the S8 protein folds around a Mg2+ ion to form an unusual tertiary structure made up of non-Watson-Crick interactions. Once bound, S8 stabilizes the interaction of other ribosomal proteins with the 16S rRNA and guides folding of the RNP subdomains to yield the mature 30S particle. 

Pubmed Search for articles by EP Nikonowicz

Select Publications

Thapar R, Denmon AP, Nikonowicz EP. Recognition modes of RNA tetraloops and tetraloop-like motifs by RNA-binding proteins.  Wiley Interdiscip Rev RNA. , 5 2014: 49-67

Davlieva, M., Donarski, J., Wang, J., Shamoo, Y. and Nikonowicz, E. P. Structure analysis of an RNA aptamer against ribosomal protein S8 from Bacillus anthracis.  Nucleic Acids Research, 42 2014: 10795-808

Sripakdeevong P, Cevec M, Chang AT, Erat MC, Ziegeler M, Zhao Q, Fox GE, Gao X, Kennedy SD, Kierzek R, Nikonowicz EP, Schwalbe H, Sigel RK, Turner DH, Das R Structure determination of noncanonical RNA motifs guided by ¹H NMR chemical shifts.  Nat Methods., 11(4) 2014: 413-6

Chang AT, Nikonowicz EP. Solution NMR determination of hydrogen bonding and base pairing between the glyQS T box riboswitch Specifier domain and the anticodon loop of tRNA(Gly).  FEBS Lett., 587(21) 2013: 3495-9

Chang, A.T. and Nikonowicz, E.P. Solution nuclear magnetic resonance analyses of the anticodon arms of proteinogenic and nonproteinogenic tRNA(Gly).  Biochemistry, 51 2012: 3662-74

Hammerstrom, T., Roh, J.H., Nikonowicz, E.P. and Koehler, T.M. Bacillus anthracis Virulence Regulator AtxA: Oligomeric state, function, and CO2-signaling.  Mol. Microbiol, 82 2011: 634-647

Denmon, A.P. Wang, J. and Nikonowicz, E.P. Conformation effects on the anticodon stem-loop of tRNATyr from Bacillus subtilis.  J. Mol. Biol., 412 2011: 285-303

Wang, J., and Nikonowicz, E.P. Solution structure of the K-turn/Specifier Loop domains from the Bacillus subtilis tyrS T box leader RNA.  J. Mol. Biol., 408 2011: 99-117

Wang, J., Henkin, T.M. and Nikonowicz, E.P. NMR Structure and Dynamics of the Specifier Domain from the Bacillus subtilis tyrS T box leader RNA.  Nucleic Acids Res., 38 2010: 3388-3398

Xia, Y., Moran, S., Nikonowicz, E.P., and Gao, X. Z-Restored spin echo 13C 1D spectrum of straight baseline free of Hump, Dip and Roll.  Mag. Reson. Chem., 46 2008: 432-435

Xia, Y., Moran, S., Nikonowicz, E.P., and Gao, X. “Z-Restored spin echo 13C 1D spectrum of straight baseline free of Hump, Dip and Roll.  Mag. Reson. Chemistry 2007In Press

Tworowska, I. and Nikonowicz, E.P. Base pairing within the ψ32, ψ39-modified anticodon arm of Escherichia coli tRNAPhe.  Journal of the American Chemical Society, 128 2007: 15571-15572

Jaroniec, C.P., Boisbouvier, J., Tworowska, I., Nikonowicz, E.P., and Bax. A. Accurate measurement of 15N-13C residual dipolar couplings in nucleic acids.  J. Biomol. NMR, 31 2005: 231-241

Boisbouvier, J., Bryce, D., O'Neil-Cabello, E., Nikonowicz, E.P., and Bax, A. Resolution-optimized NMR measurement of 1DCH, 1DCC, and 2DCH residual dipolar couplings in nucleic acid bases.  J. Biomol. NMR, 30 2005: 287-301

Cabello-Villegas, J., and Nikonowicz, E.P. Solution structure of psi32-modified anticodon stem-loop from Escherichia coli rTNAPhe.  Nucleic Acids Res., 33 2005: 6961-6971

O'Neil-Cabello, E., Wu, Z., Bryce, D., Nikonowicz, E.P., and Bax, A. Enhanced spectral resolution in RNA HCP spectra for measurement of 3JC2'P and 3JC4'P couplings and 31P chemical shift changes upon weak alignment.  J. Biomol. NMR, 30 2004: 61-70

O'Neil-Cabello, E., Bryce, D.L., Nikonowicz, E.P., and Bax, A. Local order in RNA from simultaneous measurement of dipolar couplings.  J. Amer. Chem. Soc., 126 2004: 66-67

Cabello-Villegas, J., Tworowska, I., and Nikonowicz, E.P. Metal ion stabilization of the U-turn of the A37 N6-dimethylallyl-modified anticodon stem-loop of Escherichia coli tRNAPhe.  Biochemistry, 43 2004: 55-66

Miclet,, E., O�Neil-Cabello, E., Nikonowicz, E.P., Live, D., and Bax, A. 1H-1H dipolar couplings provide a unique probe of RNA backbone structure.  Journal of the American Chemical Society 2003In Press

DeJong, E., Marzluff, W.F., and Nikonowicz, E.P. NMR structure and dynamics of the RNA binding site for the histone mRNA stem-loop binding protein.  RNA, 8 2002: 83-96

Cabello-Vellegas, J., Winkler, M.E., and Nikonowicz, E.P. Solution conformations of unmodified and A37 N6-dimethylallyl modified anticodon stem-loops of Escherichia coli tRNAPhe.  J. Mol. Biol., 319 2002: 1015-1034

Nikonowicz, E.P. Preparation of 2H-labeled RNA oligonucleotides and their use in NMR studies.  Methods Enzymol., 338 2001: 320-341

Cabello-Vellegas, J., and Nikonowicz, E.P. Detecting duplex and hairpin conformations of short oligonucleotides using chemical shifts.  Nucleic Acids. Res., 28 2000: 74-77

Zimmermann, R.A., Alimov, I., Uma, K., Wu, H., Wower, I., Nikonowicz, E.P., Drygin, D., Dong, P., and Jiang, L. How ribosomal proteins and rRNA recognize one another.  in The Ribosome: Structure, Function, Antibiotics, and Cellular Interactions, 2000: 93-104

Smith, J.S., and Nikonowicz, E.P. Phosphorothioate substitution can substantially alter RNA conformation.  Biochemistry, 39 2000: 5642-5652

Nikonowicz, E.P., and Smith, J.S. NMR Spectroscopic investigations of phosphorothioate containing RNAs.  Phosphorus, Sulfur, & Silicon, 146 1999: 305-308

  • B.S. Biology (1985) St. Louis University
  • Ph.D. Chemistry (1990) Purdue University
  • Institute of Biosciences and Bioengineering
  • Keck Center for Quantitative Biomedical Sciences
Research Areas
  • RNA-Protein biochemistry, structure, function Small molecule-RNA interactions
Professional Experience
  • NIH Postdoctoral Associate
    University of Colorado
  • Assistant Professor
    Rice University
  • Associate Professor
    Rice University
Contact Information
Email: edn@rice.edu
Phone: 713-348-4912
Office: Keck, 313