DHX9

DHX9, also known as DEAH-box helicase 9 or RNA helicase A (RHA), is a human enzyme encoded by the DHX9 gene. It is a member of the DEAH-box family of ATP-dependent RNA helicases and functions as a molecular motor that unwinds RNA duplexes and RNA:DNA hybrids.

The protein features two N-terminal double-stranded RNA-binding domains that help target structured RNA, followed by a conserved DEAH-box helicase core and additional regulatory regions. This architecture enables DHX9 to bind various RNA substrates and use ATP hydrolysis to remodel them, facilitating processes such as transcription and RNA metabolism.

DHX9 participates in transcriptional regulation by associating with RNA polymerase II and several splicing and RNA export factors. It contributes to co-transcriptional RNA processing and can influence the export of mRNA to the cytoplasm. Through these activities, DHX9 plays a multifunctional role in gene expression.

In genome stability, DHX9 is implicated in resolving R-loops and transcription-associated RNA:DNA hybrids, which helps prevent genome instability. It interacts with BRCA1 and other DNA damage response proteins, linking RNA metabolism to DNA repair pathways and maintenance of genomic integrity.

DHX9 has been reported as a host factor for several viruses, where it can be recruited to viral genomes and modulate replication or gene expression in certain systems. This underlines a role for DHX9 in host–pathogen interactions.

Cellular localization is predominantly nuclear, with evidence for regulated nucleo-cytoplasmic shuttling. DHX9 is conserved across eukaryotes and serves multiple roles at the intersection of RNA biology and genome maintenance.

Clinical relevance: altered expression or function of DHX9 has been observed in some cancers and viral infections, and the protein is a subject of study as a potential biomarker or therapeutic target.