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Synthetic strategies towards the development of new RNA structure and RNA labeling tools.

Abstract

The central dogma originally postulated that RNA solely played the role of genetic information transfer from DNA to protein. But that has been proven to be an inadequate depiction of this genetic material. RNA plays an integral role in the cell beyond just translation alone. RNA is capable of regulating every step of the central dogma. Because of this realization, the development of the RNA toolkit has been an ever-growing field. This toolkit consists of techniques to study RNA structure, localization, associated binding proteins, and nascent transcription. Herein, my studies aimed to enhance the field of RNA structure probing, as well as the field of labeling nascent RNA with bioorthogonal nucleosides. To that aim, I have synthesized a new probe with increased stability for icSHAPE structure probing of RNA. Additionally, I have synthesized the first azide containing bioorthogonal nucleosides for RNA labeling. Lastly, I extended the PGA toolkit to include pyrimidine nucleosides so that the cell-specific RNA labeling can be biased for either RNA or polyadenylated RNA, based on the nucleoside being used.

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