RNA and RNA-protein interactions play a key role in many biological processes and diseases. Although, the majority of drugs target cellular, bacterial or viral proteins known to be associated with a particular human disease, some already existing highly efficient medications interact with RNA or RNA-protein complexes. A better understanding of RNA structure would provide access to design and optimization of new drugs targeting RNA. The emphasis of my research proposal is on the X-ray crystallographic determination of key RNA structures and their complexes. The proposal is subdivided into two major projects: antibiotic-human mitochondrial ribosomal decoding site recognition, and structure of the key domains of human telomerase RNA. The goal of the first project is to evaluate the structures of human mitochondrial ribosomal decoding site and aminoglycoside antibiotics induced deafness-associated mutant, both alone and in a complex with aminoglycosides. The available structural literature is focused on the prokaryotic decoding site and its complexes. The goal of the second project is to solve the structure of four crucial domains of human telomerase RNA and congenital dyskeratosis syndrome-associated mutants that, if successful, could provide deep insights into telomerase structure and function.
| Rechkoblit, Olga; Malinina, Lucy; Cheng, Yuan et al. (2009) Impact of conformational heterogeneity of OxoG lesions and their pairing partners on bypass fidelity by Y family polymerases. Structure 17:725-36 |
| Zhang, Ling; Rechkoblit, Olga; Wang, Lihua et al. (2006) Mutagenic nucleotide incorporation and hindered translocation by a food carcinogen C8-dG adduct in Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4): modeling and dynamics studies. Nucleic Acids Res 34:3326-37 |
| Rechkoblit, Olga; Malinina, Lucy; Cheng, Yuan et al. (2006) Stepwise translocation of Dpo4 polymerase during error-free bypass of an oxoG lesion. PLoS Biol 4:e11 |
