2009 Rustbelt RNA Meeting
RRM

 

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Poster abstracts

Poster number 87 submitted by Shu Zhou

Identification of small compounds as inhibitors for tRNA-T Box antiterminator interaction

Shu Zhou (Chemistry and Biochemistry, Ohio University), George Acquaa-Harrison (Chemistry and Biochemistry, Ohio University), Iwona Maciagiewicz (Chemistry and Biochemistry, Ohio University), Crina Orac (Chemistry and Biochemistry, Ohio University), Abijit Nayek (Chemistry and Biochemistry, Ohio University), Stephen Bergmeier, Jennifer Hines (Chemistry and Biochemistry, Ohio University)

Abstract:
The T box transcription antitermination riboswitch regulates gene expression by interaction of uncharged cognate tRNA with the 5′ untranslated region of the mRNA during transcription. This interaction involves, in part, the base pairing of the tRNA accepter end with four bases in the bulge region of the T box antiterminator element, which prevents the formation of an alternative terminator element and results in complete transcription of the gene. In an effort to investigate the potential for molecular modulation of this mechanism, we developed a fluorescence anisotropy screening essay to identify ligands that can disrupt the tRNA-T Box antiterminator interactions in a model system. Two sets of small molecules were investigated and the interaction between the lead compounds and T Box antiterminator was studied in more details using Fluorescence Resonance Energy Transfer (FRET) and enzymatic probing.

Keywords: T box transcription antitermination, Fluorescence anisotropy, Small molecule inhibitors