Multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3' to 5' direction and that plays important roles in many processes, such as DNA replication, transcriptional activation, post-transcriptional RNA regulation, mRNA translation and RNA-mediated gene silencing (PubMed:7511411). Requires a 3'-single-stranded tail as entry site for acid nuclei unwinding activities as well as the binding and hydrolyzing of any of the four ribo- or deoxyribo-nucleotide triphosphates (NTPs) (PubMed:7511411). Unwinds numerous nucleic acid substrates such as double-stranded (ds) DNA and RNA, DNA:RNA hybrids, DNA and RNA forks composed of either partially complementary DNA duplexes or DNA:RNA hybrids, respectively, and also DNA and RNA displacement loops (D- and R-loops), triplex-helical DNA (H-DNA) structure and DNA and RNA-based G-quadruplexes (PubMed:7511411). Binds dsDNA, single-stranded DNA (ssDNA), dsRNA, ssRNA and poly(A)-containing RNA (PubMed:7511411). Binds also to circular dsDNA or dsRNA of either linear and/or circular forms and stimulates the relaxation of supercoiled DNAs catalyzed by topoisomerase TOP2A. Plays a role in DNA replication at origins of replication and cell cycle progression. Plays a role as a transcriptional coactivator acting as a bridging factor between polymerase II holoenzyme and transcription factors or cofactors, such as BRCA1, CREBBP, RELA and SMN1. Binds to the CDKN2A promoter. Plays several roles in post-transcriptional regulation of gene expression. In cooperation with NUP98, promotes pre-mRNA alternative splicing activities of a subset of genes. As component of a large PER complex, is involved in the negative regulation of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms. Acts also as a nuclear resolvase that is able to bind and neutralize harmful massive secondary double-stranded RNA structures formed by inverted-repeat Alu retrotransposon elements that are inserted and transcribed as parts of genes during the process of gene transposition. Involved in the positive regulation of nuclear export of constitutive transport element (CTE)-containing unspliced mRNA. Component of the coding region determinant (CRD)-mediated complex that promotes cytoplasmic MYC mRNA stability. Plays a role in mRNA translation. Positively regulates translation of selected mRNAs through its binding to post-transcriptional control element (PCE) in the 5'-untranslated region (UTR). Involved with LARP6 in the translation stimulation of type I collagen mRNAs for CO1A1 and CO1A2 through binding of a specific stem-loop structure in their 5'-UTRs. Stimulates LIN28A-dependent mRNA translation probably by facilitating ribonucleoprotein remodeling during the process of translation. Plays also a role as a small interfering (siRNA)-loading factor involved in the RNA-induced silencing complex (RISC) loading complex (RLC) assembly, and hence functions in the RISC-mediated gene silencing process. Binds preferentially to short double-stranded RNA, such as those produced during rotavirus intestinal infection. This interaction may mediate NLRP9 inflammasome activation and trigger inflammatory response, including IL18 release and pyroptosis. Finally, mediates the attachment of heterogeneous nuclear ribonucleoproteins (hnRNPs) to actin filaments in the nucleus. ATP + H2O = ADP + H(+) + phosphate Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1. Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active). Associates (via DRBM domains) with the RISC complex; this association occurs in a small interfering (siRNA)-dependent manner. Associates with the SMN complex; this association induces recruitment of DHX9 to the RNA polymerase II. Associates with polysomes in a LIN28A-dependent manner. Interacts (via C-terminus) with ACTB; this interaction is direct and mediates the attachment to nuclear ribonucleoprotein complexes. Interacts with ADAR isoform 1; this interaction occurs in a RNA-independent manner. Interacts (via DRBM domains) with AGO2 (via middle region); this interaction promotes active RISC assembly by promoting the association of siRNA with AGO2. Interacts (via NTD domain) with AKAP8L (via N-terminus). Interacts with BRCA1 (via C-terminus); this interaction is direct and links BRCA1 to the RNA polymerase II holoenzyme. Interacts (via N-terminus) with CREBBP; this interaction mediates association with RNA polymerase II holoenzyme and stimulates CREB-dependent transcriptional activation. Interacts (via N-terminus) with EIF2AK2/PKR; this interaction is dependent upon the activation of the kinase. Interacts (via DRBM domains) with DICER1. Interacts with H2AX; this interaction is direct, requires phosphorylation of histone H2AX by PRKDC and promotes binding of DHX9 to transcriptionally stalled sites on chromosomal DNA in response to genotoxic stress. Interacts with HNRNPC; this interaction is direct, enhanced probably by their concomitant binding to RNA and mediates the attachment to actin filaments. Interacts (via NTD domain) with PRMT1. Interacts with IGF2BP1. Interacts with IGF2BP2, IGF2BP3. Interacts (via DRBM domains) with ILF3; this interaction occurs in a RNA-independent manner. Interacts with Importin alpha/Importin beta receptor. Interacts with LARP6 (via C-terminus); this interaction occurs in a mRNA-independent manner. Interacts (via N- and C-terminus) with LIN28A (via C-terminus); this interaction occurs in a RNA-independent manner. Interacts with LMX1B. Interacts (via helicase C-terminal domain, HA2 and OB-fold regions) with MAVS (via CARD domain); this interaction occurs in both resting and double-stranded RNA poly(I:C)-induced cells. Interacts with MBD2; this interaction stimulates transcriptional activation in a CREB-dependent manner. Interacts (via H2A and OB-fold regions) with MYD88 (via TIR domain); this interaction is direct. Interacts with NLRP9 upon rotavirus infection; this interaction may trigger NLRP9 inflammasome activation and inflammatory response. Interacts (via DRBM, OB-fold and RGG regions) with NUP98 (via N-terminus); this interaction occurs in a RNA-dependent manner and stimulates DHX9-mediated ATPase activity and regulates transcription and splicing of a subset of genes. Interacts (via N-terminus) with NXF1 (via N-terminus); this interaction is direct and negatively regulates NXF1-mediated nuclear export of constitutive transport element (CTE)-containing cellular mRNAs. Interacts with RELA; this interaction is direct and activates NF-kappa-B-mediated transcription. Interacts (via MTAD region) with RNA polymerase II holoenzyme; this interaction stimulates transcription activation in a CREB-dependent manner. Interacts (via RGG region) with SMN1; this interaction links SMN1 to the RNA polymerase II holoenzyme (ref.8). Interacts with SP7. Interacts (via DRBM domains) with TARBP2 (via DRBM first and second domains); this interaction occurs in a small interfering (siRNA)-dependent manner. Interacts with TOP2A; this interaction occurs in a E2 enzyme UBE2I- and RNA-dependent manner, negatively regulates DHX9-mediated double-stranded DNA and RNA duplex helicase activity and stimulates TOP2A-mediated supercoiled DNA relaxation activity. Interacts (via DRBM domains and C-terminus) with WRN (via 3'-5' exonuclease domain); this interaction inhibits the DNA-dependent NTPase and DNA helicase activities of DHX9 and stimulates the 3'-5' exonuclease activity of WRN. Interacts with XRCC5; this interaction occurs in a RNA-dependent manner. Interacts with ZIC2 (via C2H2-type domain 3). Interacts with MCM3AP (By similarity). Nucleoplasmic shuttling protein. Its nuclear import involves the nucleocytoplasmic transport receptor Importin alpha/Importin beta receptor pathway in a Ran-dependent manner. In interphase, localizes in nuclear stress granules and at perichromatin fibrils and in cytoplasmic ribonucleoprotein granules. Colocalizes with WRN and H2AX at centrosomes in a microtubule-dependent manner following DNA damaging agent treatment. Excluded from the mitotic nucleus as early as prophase and re-entered the nucleus at telophase. Recruited in diffuse and discrete intranuclear foci (GLFG-body) in a NUP98-dependent manner. Colocalizes with SP7 in the nucleus. Colocalizes with ACTB at nuclear actin filaments inside the nucleus or at the nuclear pore. Colocalizes with HNRNPC at nuclear ribonucleoprotein complex proteins in the nucleus. Localized in cytoplasmic mRNP granules containing untranslated mRNAs. DRBM domains cooperate for the binding to nucleic acid but not for unwinding helicase activity. The helicase-associated domain-2 (HA2) region is essential for the duplex RNA unwinding helicase activity. The minimal transactivation region (MTAD) mediates interaction with the RNA polymerase II holoenzyme and stimulates transcriptional activation in a CREB-dependent manner. The oligonucleotide- or oligosaccharide-binding (OB-fold) and the repeated arginine and glycine-glycine (RGG) regions are dispensable for both RNA-binding and unwinding helicase activities. The RGG region contains both nuclear localization signal (NLS) and nuclear export signal (NES) and is necessary and sufficient for nucleocytoplasmic shuttling in a RNA-independent manner. Methylated. PRMT1-mediated methylation of undefined Arg residues in the nuclear transport domain (NTD) is required for nuclear import of DHX9. Phosphorylated by PRKDC; phosphorylation occurs in a RNA-dependent manner. Phosphorylated by EIF2AK2/PKR; this phosphorylation reduces its association with double-stranded RNA. Belongs to the DEAD box helicase family. DEAH subfamily.