Molecular Cell: DICER Ribonuclease Removes Harmful R-Loops (Sung)

Lola P. Camino 1 2 4, Arijit Dutta 3 4, Sonia Barroso 1 2, Carmen Pérez-Calero 1 2, Jeffrey N. Katz 3, María García-Rubio 1 2, Patrick Sung 3, Belén Gómez-González 1 2, Andrés Aguilera 1 2 5

Highlights
•DICER RNase activity mediates R-loop processing in vitro and in cells
•DICER binds R-loops readily but not DNA-RNA hybrids
•DICER cleaves the RNA moiety of DNA-RNA hybrids within R-loop structures
•DICER overexpression counteracts harmful nuclear DNA-RNA hybrids

Summary
R-loops, consisting of a DNA-RNA hybrid and a displaced DNA strand, 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 explicitly cleaving the RNA within R-loops. Notably, a DICER RNase mutant impaired in R-loop processing causes a substantial 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 maintaining genome integrity in higher eukaryotes.

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