DICER ribonuclease removes harmful R-loops

Lola P. Camino, Arijit Dutta, Sonia Barroso, Carmen Pérez-Calero, Jeffrey N. Katz, María García-Rubio, Patrick Sung, Belén Gómez-González, Andrés Aguilera

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3707-3719.e5
JournalMolecular Cell
Volume83
Issue number20
DOIs
StatePublished - Oct 19 2023

Keywords

  • DICER
  • DICER1 syndrome
  • DNA damage
  • R-loops
  • RNA nuclease
  • genetic instability
  • replication fork stalling

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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