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

Prasun Chakraborty, Jeffrey Huang, Kevin Hiom (Lead / Corresponding author)

Research output: Contribution to journalArticle

9 Citations (Scopus)
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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 PolII 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.
Original languageEnglish
Article number4346
Pages (from-to)1-14
Number of pages14
JournalNature Communications
Volume9
Issue number9
DOIs
Publication statusPublished - 19 Oct 2018

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