R-Loops as Cellular Regulators and Genomic Threats

Mol Cell. 2019 Feb 7;73(3):398-411. doi: 10.1016/j.molcel.2019.01.024.


During transcription, the nascent RNA strand can base pair with its template DNA, displacing the non-template strand as ssDNA and forming a structure called an R-loop. R-loops are common across many domains of life and cause DNA damage in certain contexts. In this review, we summarize recent results implicating R-loops as important regulators of cellular processes such as transcription termination, gene regulation, and DNA repair. We also highlight recent work suggesting that R-loops can be problematic to cells as blocks to efficient transcription and replication that trigger the DNA damage response. Finally, we discuss how R-loops may contribute to cancer, neurodegeneration, and inflammatory diseases and compare the available next-generation sequencing-based approaches to map R-loops genome wide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Nucleus / physiology*
  • DNA / chemistry
  • DNA / genetics*
  • DNA / metabolism
  • DNA Damage
  • DNA Repair
  • Gene Expression Regulation
  • Genome*
  • Genomic Instability*
  • Humans
  • Nucleic Acid Conformation
  • Nucleic Acid Heteroduplexes / chemistry
  • Nucleic Acid Heteroduplexes / genetics*
  • Nucleic Acid Heteroduplexes / metabolism
  • RNA / chemistry
  • RNA / genetics*
  • RNA / metabolism
  • Structure-Activity Relationship
  • Transcription, Genetic


  • Nucleic Acid Heteroduplexes
  • RNA
  • DNA