Talk abstracts

Talk on Saturday 08:30-08:45am submitted by Jun Jiang

Structure Modulation of Helix 69 from 23S rRNA by Pseudouridylation

Jun Jiang (Department of Chemistry, Wayne State University), Raviprasad Aduri (Institute for Bioscience and Biotechnology, University of Maryland), Christine S. Chow (Department of Chemistry, Wayne State University), John SantaLucia, Jr. (Department of Chemistry, Wayne State University)

Abstract:
Helix 69 (H69) is a 19-nucleotide stem-loop segment in bacterial 23S ribosomal RNAs (rRNAs). The sequence, secondary structure, and the post-transcriptional modifications are highly conserved. Being part of a key intersubunit bridge, B2a, and interacting with multiple translational factors during protein synthesis, H69 has become an attractive target for new antibiotics. It was shown through biophysical and biochemical studies that pseudouridine modifications confer effects on both the structure and function of H69; however, the structural effects of pseudouridylation are difficult to assess without a structure of the unmodified H69. In this project, the structures of unmodified and pseudouridylated H69s in aqueous solution were solved by nuclear magnetic resonance spectroscopy. Comparison of the two structures suggests that profound conformational changes are induced by pseudouridylations, and modifications at the three sites (1911, 1915, and 1917, E. coli numbering) work synergistically to modulate H69 folding. Results from this research not only provide insight into the structural effects of pseudouridylations on RNA folding, but also establish a platform to explore the binding patterns between the H69s, unmodified and pseudouridylated, and potential antibiotic candidates.

Keywords: RNA, pseudouridine, structure