When R-Loops Go Awry: Genome Instability and Neurological Diseases

The basic structure of DNA is a double helix formed by base pairing between complementary strands. However, during transcription, RNA hybridizes with the template DNA, whereas the complementary DNA strand becomes displaced and remains unpaired. This process forms a DNA-RNA hybrid structure known as an R-loop; similar structures can also occur in a non-co-transcriptional manner. In recent years, R-loops have been reported to be involved in various cellular functions. However, when not properly regulated, they can compromise genomic DNA stability. R-loops play roles in gene expression, DNA replication, and transcription termination. Dysregulation of R-loop homeostasis has been implicated in various human diseases, including neurological diseases. In this review, we discuss the physiological and pathological roles of R-loops, their related regulatory mechanisms controlling their formation and resolution, and their association with neurological diseases.