Out of Balance: R-loops in Human Disease
Figure 3
Potential R-loop-based therapeutic approach in Angelman Syndrome (AS).
A. Neuronal expression of the paternal ncRNA Ube3a-ATS represses paternal Ube3a gene in cis [101]. DNA methylation of the Snord116 locus on the maternal allele prevents Ube3a-ATS transcription, resulting in Ube3a expression from the maternal allele. Transcriptional repression is indicated by red crosses. B. R-loop-mediated re-activation of silent paternal Ube3a gene provides a targeted therapy for AS. Deletion leading to the loss of maternal Ube3a expression detected in AS is indicated by the red dashed line. Topotecan treatment increases R-loop levels over the Snord116 locus, resulting in chromatin decondensation, inhibition of Pol II transcription through Ube3a-ATS, and increased expression of Ube3a from the paternal allele [50].