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DHX9 helicase promotes R-loop formation in cells with impaired RNA splicing.

ABSTRACT: R-loops are stable nucleic acid structures that have important physiological functions, but which also pose a significant threat to genomic stability. Increased R-loops cause replication stress and chromosome fragility and have been associated with diseases such as neurodegeneration and cancer. Although excessive R-loops are a feature of cells that are defective in RNA processing, what causes them to form is unclear. Here, we demonstrate that DHX9 (RNA helicase A) promotes the formation of pathological and non-pathological R-loops. In the absence of splicing factors, formation of R-loops correlates with the prolonged association of DHX9 with RNA Polymerase II (RNA Pol II). This leads to the production of DNA-RNA hybrid, which traps RNA Pol II on chromatin with the potential to block DNA replication. Our data provide a molecular mechanism for the formation of R-loops that is relevant to neurodegenerative diseases and cancers in which deregulated RNA processing is a feature.

SUBMITTER: Chakraborty P

PROVIDER: S-EPMC6195550 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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DHX9 helicase promotes R-loop formation in cells with impaired RNA splicing.

Chakraborty Prasun P Huang Jeffrey T J JTJ Hiom Kevin K

Nature communications 20181019 1

R-loops are stable nucleic acid structures that have important physiological functions, but which also pose a significant threat to genomic stability. Increased R-loops cause replication stress and chromosome fragility and have been associated with diseases such as neurodegeneration and cancer. Although excessive R-loops are a feature of cells that are defective in RNA processing, what causes them to form is unclear. Here, we demonstrate that DHX9 (RNA helicase A) promotes the formation of patho ...[more]

PMID: 30341290

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TDRD3 promotes DHX9 chromatin recruitment and R-loop resolution

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| S-EPMC6663884 | biostudies-literature

Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9).

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| S-EPMC3597700 | biostudies-literature

The DNA/RNA helicase DHX9 contributes to the transcriptional program of the androgen receptor in prostate cancer.

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| S-EPMC9118622 | biostudies-literature

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