ATP-dependent RNA helicase A

ATP-dependent RNA helicase A (DHX9) is a multifunctional nucleic acid helicase that unwinds DNA and RNA in the 3' to 5' direction (UniProt: Q08211). It plays critical roles in DNA replication, transcriptional activation, post-transcriptional RNA regulation, mRNA translation, and RNA-mediated gene silencing. The protein binds diverse nucleic acid substrates including double-stranded DNA/RNA, DNA:RNA hybrids, and G-quadruplexes, and functions as a transcriptional coactivator bridging RNA polymerase II to transcription factors.

DHX9 is involved in multiple cellular processes including alternative splicing, circadian rhythm regulation, nuclear export of mRNA, and inflammasome activation during viral infection (UniProt: Q08211). A pathogenic variant association has been documented with autosomal dominant intellectual developmental disorder 75 (MRD75, MIM: 620988), which presents with developmental delay, intellectual disability, and autism spectrum disorder features among other neuropsychiatric manifestations.

DHX9 is downregulated in Alzheimer's disease brain tissue (Chaparral AD proteomics). Analysis of post-mortem AD brain versus age-matched controls using tandem mass tag proteomics across four subcellular fractions revealed a mean log2 fold-change of −0.221, indicating modest but consistent reduced expression in the disease state.