Project Summary/Abstract
Epitranscritomics is the study of RNA modifications, which include more than 170 naturally occurring chemical
alternations to the nucleotides. More than 60 are found in human RNA of all types: mRNA, tRNA, rRNA, lncRNA,
and the others. These modifications are dynamic; their global quantities change in development and during
disease progression. They are installed by writer enzymes, read by reader proteins and removed by eraser
enzymes, and they have an intrinsic capacity to alter RNA structure and dynamics. They influence translation
initiation and termination, translation fidelity, alternative splicing, trafficking between cellular compartments, and
regulate RNA degradation. RNA reader, writer and eraser proteins are promising drug targets of high current
interest to pharma. In this project, we will develop and commercialize a new approach to detecting, identifying,
and mapping, RNA modifications in a multiplex and with high sensitivity—suitable for clinical samples (e.g.
needle biopsies, FFPE samples) in which only sub-nanogram quantities of RNA may be available. This
technology will be significant because it will provide the first commercial method for profiling and correlating
changes of multiple RNA modification types across the entire transcriptome using low sample input.