RNA-Loops (DNA/RNA Hybrids) Mechanisms, Genomic and Cellular Roles-A Review with Emphasis on Neuropsychiatric Diseases

Abstract

RNAs adopt heterogenous folded structures that are essential for function and thus play critical roles in cellular biology. An example of this is the ribosome, a complex, three-dimensionally folded macromolecular machine that coordinates protein synthesis. Advances in RNA biochemistry, structural and molecular biology, and bioinformatics have unveiled other non-coding RNAs whose functions are dictated by their structure. It is not surprising that aberrantly folded RNA structures enable disease. R-loops are nucleic acid structures encompassing an RNA-DNA hybrid and a displaced single-stranded DNA (ssDNA) (Hegazy et al., 2019). Once thought to be uncommon transcriptional byproducts, but reclassified as prevalent and functionally significant in a variety of eukaryotic and prokaryotic species. During transcription, R-loops naturally form when the developing RNA hybridizes with the DNA template strands; displacing the non-template strand and creating a three-stranded structure. RNA loops are fundamental secondary structural elements that play crucial roles in RNA function and interaction within cells. Recent developments in immunoprecipitation techniques (e.g., DRIP-seq) and high-throughput sequencing have made it possible to profile R-loops throughout the genome, demonstrating their occurrence in both coding and non-coding areas. The RNA loops are involved in a wide range of biological processes spanning genome regulation, physiology and repair. Mounting evidence also supports R-loop deregulation as a frequent, initiating, event during the development of several human pathologies, such as cancer and neurological disorder. Several applications of RNAloop in biomedical research, clinical and diagnostics underscores their application potential. With this background, we update the current available literature nd review diverse aspects of RNAloops traversing from their roles in cell biology and physiology, genome regulation and instability, the cellular mechanisms and methods of detection. Finally, we in detail curate literature of their roles in Human diseases with emphasis on neurodegenerative diseases.