DICER ribonuclease removes harmful R-loops

Mol Cell. 2023 Oct 19;83(20):3707-3719.e5. doi: 10.1016/j.molcel.2023.09.021. Epub 2023 Oct 11.


R-loops, which consist of a DNA-RNA hybrid and a displaced DNA strand, are known to threaten genome integrity. To counteract this, different mechanisms suppress R-loop accumulation by either preventing the hybridization of RNA with the DNA template (RNA biogenesis factors), unwinding the hybrid (DNA-RNA helicases), or degrading the RNA moiety of the R-loop (type H ribonucleases [RNases H]). Thus far, RNases H are the only nucleases known to cleave DNA-RNA hybrids. Now, we show that the RNase DICER also resolves R-loops. Biochemical analysis reveals that DICER acts by specifically cleaving the RNA within R-loops. Importantly, a DICER RNase mutant impaired in R-loop processing causes a strong accumulation of R-loops in cells. Our results thus not only reveal a function of DICER as an R-loop resolvase independent of DROSHA but also provide evidence for the role of multi-functional RNA processing factors in the maintenance of genome integrity in higher eukaryotes.

Keywords: DICER; DICER1 syndrome; DNA damage; R-loops; RNA nuclease; genetic instability; replication fork stalling.

Publication types

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

MeSH terms

  • DNA
  • DNA Helicases / genetics
  • DNA Replication
  • Genomic Instability
  • Humans
  • R-Loop Structures* / genetics
  • RNA / genetics
  • Ribonuclease H / genetics
  • Ribonuclease H / metabolism
  • Ribonucleases* / genetics


  • Ribonucleases
  • RNA
  • DNA
  • DNA Helicases
  • Ribonuclease H