DICER 核糖核酸酶可清除有害 R 环。
DICER ribonuclease removes harmful R-loops.
机构信息
Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla, CSIC, 41092 Seville, Spain; Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Seville, Spain.
Greehey Children's Cancer Research Institute, Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
出版信息
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.
R 环由 DNA-RNA 杂合体和一条链位移的 DNA 组成，已知其会威胁基因组的完整性。为了对抗这种情况，不同的机制通过阻止 RNA 与 DNA 模板杂交（RNA 生物发生因子）、解旋杂交体（DNA-RNA 解旋酶）或降解 R 环的 RNA 部分（H 型核糖核酸酶[RNase H]）来抑制 R 环的积累。到目前为止，RNase H 是已知唯一能够切割 DNA-RNA 杂合体的核酶。现在，我们表明 RNase DICER 也能解决 R 环问题。生化分析表明，DICER 通过特异性切割 R 环内的 RNA 起作用。重要的是，一种在 R 环加工中受损的 DICER RNase 突变体导致细胞中 R 环的强烈积累。因此，我们的结果不仅揭示了 DICER 作为一种独立于 DROSHA 的 R 环解旋酶的功能，还为多功能 RNA 加工因子在高等真核生物中维持基因组完整性的作用提供了证据。
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