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DICER ribonuclease removes harmful R-loops.

Authors :
Camino LP
Dutta A
Barroso S
Pérez-Calero C
Katz JN
García-Rubio M
Sung P
Gómez-González B
Aguilera A
Source :
Molecular cell [Mol Cell] 2023 Oct 19; Vol. 83 (20), pp. 3707-3719.e5. Date of Electronic Publication: 2023 Oct 11.
Publication Year :
2023

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.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2023 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1097-4164
Volume :
83
Issue :
20
Database :
MEDLINE
Journal :
Molecular cell
Publication Type :
Academic Journal
Accession number :
37827159
Full Text :
https://doi.org/10.1016/j.molcel.2023.09.021