Dynamic chemical modifications on RNAs have been discovered to play critical regulatory roles in gene regulation, cellular processes and human diseases including cancers. However, the definite roles of these modifications and underlying mechanisms in their involvement in gene regulation and disease processes remain elusive due to the complexity of epitranstriptomic regulation and the lack of proper enabling tools. To address these limitations, we propose to develop new technologies that enable the editing of specific RNA modifications, including N6-methyladenosine (m6A) and 5-methylcytosine (m5C), on specific endogenous messenger RNA (mRNA) transcripts. We will combine the RNA-targeting CRISPR method and the chemically induced proximity technology to achieve spatiotemporal specific epitranscriptome editing. We expect this new technology will significantly facilitate the research of RNA epigenetics in cancer and may lead to the development of new cancer therapies resulted from erroneous RNA modifications.
Dynamic RNA modifications have been discovered as a new layer of epigenetic regulation and involved in several human diseases including cancers. This proposal is to develop new enabling technologies to edit chemical modifications on messenger RNAs that will facilitate functional of these modifications in cells. We expect the results from this research will advance our understanding of gene regulation and lead to the development of new therapeutic strategies for cancers and other human diseases.
