CRISPR screening reveals that RNA helicase DDX41 triggers ribosome biogenesis and cancer progression through R-loop-mediated RPL/RPS transcription

Our findings showed that high-expressed DDX41 translocates to the R-loop structure of RPL/RPS genes, accelerating their transcription and promoting ribosome biogenesis. Additionally, acetyltransferase KAT8 is required for H3K9ac modification of the DDX41 promoter, while NR2C1/NR2C2 are responsible for regulating DDX41 transcription. Whole-transcriptome sequencing (RNA-Seq) was performed to identify the downstream target genes regulated by DDX41 in HUH7 cells. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) of DDX41 and R-ChIP-seq to identify the distribution of DDX41 or R-loops in genome of HUH7 cells. ChIP-seq of H3K9ac, KAT8, NR2C1 and NR2C2 to identify the enrichment of KAT8, NR2C1 and NR2C2 on DDX41 promoter region of HUH7 cells.