RNA is an extremely versatile biomolecule, which is capable of folding into specific tertiary structures and interacting with many other RNAs and proteins in diverse and yet specific ways. We employ an integrated approach of biochemical and solution structural studies by nuclear magnetic resonance (NMR) spectroscopy to reveal the structure and function of biologically important RNA molecules.

Our main research focus is internal ribosome entry site (IRES) RNAs, which are used by many RNA viruses to hijack the eukaryotic translational machinery. Translation of the Hepatitis C viral (HCV) RNA genome is initiated upon specific interactions of the IRES RNA with the small ribosomal 40S subunit and initiation factors. We have solved the structure of a 25kDa subunit of the IRES RNA, which modulates 40S conformation and thereby mediates release of initiation factors during 80S ribosome formation.

We are currently studying several cellular and viral IRES RNAs and their interactions with the translational machinery to reveal the underlying principles of IRES-mediated initiation.

Lukavsky, P.J., Otto, G.A., Kim, I. & Puglisi, J.D. (2003)
Structure of HCV IRES domain II determined by NMR.
Nature Struct. Biol. 12, 1033-1038.

Locker, N., Easton, L.E. & Lukavsky, P.J. (2006)
Affinity purification of eukaryotic 48S initiation complexes.
RNA 12, 683-690.

Tzakos, A.G., Grace, C.R., Lukavsky, P.J. & Riek, R. (2006)
NMR techniques for very large proteins and RNAs in solution.
Annu. Rev. Biophys. Biomol. Struct. 35, 319-342.