DICER ribonuclease removes harmful R-loops
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...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad de Sevilla (US) |
| Repositorio: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:dnet:idus________::88144c45111e16de4707a268d7562fe8 |
| Acceso en línea: | https://hdl.handle.net/11441/185491 https://doi.org/10.1016/j.molcel.2023.09.021 |
| Access Level: | acceso abierto |
| Palabra clave: | Genetic instability R-loops DICER RNA nuclease |
| Sumario: | 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 (RNases H). Thus far, type H RNases 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 multifunctional RNA processing factors in the maintenance of genome integrity in higher eukaryotes. |
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