Targeting non-coding RNAs as a novel method to control DNA repair and treatment response

Emerging evidence, including preliminary findings of our own, indicates that RNA plays an important role in regulating DNA repair and genome stability, but the specific RNAs involved, underlying mechanism(s) and therapeutic implications remain largely unclear.

Here, we postulate the existence of a network of RNAs that participate in DNA repair by regulating repair enzymes and whose dysfunction could contribute to the development of various diseases, including cancer.To test this exciting hypothesis, we have assembled a close-knit team with highly complementary expertise in RNA biology, DNA repair, disorders caused by genomic instability and murine models, all of whom have direct access to state-of-the-art infrastructure.Utilizing a combination of biochemical methods, RNA epigenomics, single-molecule microscopy, and functional DNA repair assays, we will (i) identify and characterize the role of specific RNAs involved in regulating DNA repair and associated enzymes; (ii) determine the impact of RNA modifications in this context; and (iii) investigate whether synthetic RNAs designed to restore or block cancer-associated RNAs can provide a novel approach to improving cancer treatment.This research will provide comprehensive knowledge concerning the role of RNA in in the repair of DNA damage in health and disease and thereby help pave the way for novel therapeutic interventions based on targeting specific RNAs.