Multiplexed Analysis of the Epitranscriptome

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Project Summary/Abstract More than 170 naturally occurring chemical modifications to RNA are known, more than 100 of which are found in human RNA of all types: mRNA, tRNA, rRNA, lncRNA, and the others. These modifications play a central role in nearly all aspects of RNA function, such as translation initiation and termination, translation fidelity, alternative splicing, trafficking between cellular compartments, and regulating RNA degradation. Proteins that install, read, and remove modifications are promising drug targets of high current interest to pharma. Currently available analytical methods either do not report on sequence context or provide sequence information but at the expense of multiplexing capability. Despite these limitations, it is now known that modifications are dynamically tied to phenotypic changes in cancer progression, drug resistance, and viral infection. The focus of this application is to de-risk a new approach to RNA modification analysis capable of reading any set of RNA modifications in a multiplexed reaction, approaching single base resolution. This technology will be significant because it will provide the first method for profiling and correlating changes of multiple RNA modification types across the entire transcriptome in a given sample.