Possible role of human ribonuclease dicer in the regulation of R loops.

Abstract

R loops are three-stranded nucleic acid structures that form naturally in cells under various conditions, mainly as intermediates during replication or as by-products during transcription. R loops are involved in the regulation of many important cellular processes, including replication, transcription, centromere stabilization, protection of chromosome ends, or control of telomere length. Unscheduled R loops are linked to many diseases, including cancer, neurodegenerative, or inflammatory disorders. The list of cancer diseases linked to excessive R loop accumulation is growing rapidly. There is currently much debate about the understanding of abnormal R loop formation and its impact on genome instability and cancer development. In this review, we briefly describe the nature of R loops, their formation under physiological and pathological conditions, and the proteins involved in the regulation of R loops. In addition, we emphasize the possible role of the human ribonuclease Dicer, a multi-tasking protein mostly known for its important role in microRNA biogenesis, in the regulation of R loops. We also discuss the involvement of R loops in cancer development and their potential use as diagnostic biomarkers. Knowledge of the molecular mechanisms underlying R loop dysregulation may significantly improve our understanding of cancer biology and provide new directions for research.