DHX9 (DEAH (Asp-Glu-Ala-His) box polypeptide 9)
2009-07-01 Frédéric Guénard , Francine Durocher AffiliationCancer Genomics Laboratory, Oncology, Molecular Endocrinology Research Centre, CRCHUL, CHUQ, Laval University, Québec, G1V 4G2, Canada
DNA/RNA
Description
The gene spans 48.5 kb and is composed of 27 exons.
Transcription
Transcription start is 163 bp upstream of first ATG of the DHX9 ORF. The translation start site is located in exon 2 and there is a sole isoform ubiquitously expressed.
Pseudogene
DHX9 pseudogene (DHX9P) is located at 13q22.
Proteins
Structure of DHX9. dsRBD, double-stranded RNA binding domain; RGG, arginine and glycine-rich region; NTD, nuclear transport domain.
Description
Monomeric 140 kDa protein. Human DHX9 is 1270 amino acids. It contains an helicase catalytic domain flanked by two double-stranded RNA binding domains (dsRBD) at the N-terminus and an RGG-box at the C terminus. A bidirectional nuclear transport domain is located at the C terminus.
Expression
All tissues tested, ubiquitous expression.
Localisation
DHX9 shuttles between the nucleus and the cytoplasm.
Function
DHX9 is a nucleic-acid helicase that unwinds double-stranded DNA and RNA in a nucleotide dependent manner. It acts as a transcriptional coactivator which stimulates transcription by interacting with the transcriptional coactivator CBP/p300, the breast cancer protein BRCA1, the RNA polymerase II and has an important role in the assembly of STAT6 transcriptosome.
DHX9 plays a role in regulating chromatin structure by interacting physically and functionally with topoisomerase IIa.
It mediates the attachment of nuclear ribonucleoprotein complexes to actin filaments, which may be related to RNA processing and transport. DHX9 interacts with the survival motor neuron which plays a role in the assembly and regeneration of small nuclear ribonucleoproteins and spliceosomes.
DHX9 acts as a nuclear shuttle protein promoting the export of mRNA transcripts through binding to TAP and HAP95.
In the cytoplasm, DHX9 is preferentially associated with actively translating polyribosomes and is necessary for efficient translation of RNAs that contain a highly structured 5UTR.
DHX9 might be necessary for maintaining genomic stability as it plays a role in promoting the DNA processing function of WRN. Overexpression of a truncated DHX9 peptide prevents normal BRCA1 function, such as BRCA1 association with nuclear foci following DNA damage. DHX9 associates with gH2AX after DNA damage, suggesting a role for DHX9 in DNA repair.
DHX9 is also necessary for early embryonic development in mice.
DHX9 plays a role in regulating chromatin structure by interacting physically and functionally with topoisomerase IIa.
It mediates the attachment of nuclear ribonucleoprotein complexes to actin filaments, which may be related to RNA processing and transport. DHX9 interacts with the survival motor neuron which plays a role in the assembly and regeneration of small nuclear ribonucleoproteins and spliceosomes.
DHX9 acts as a nuclear shuttle protein promoting the export of mRNA transcripts through binding to TAP and HAP95.
In the cytoplasm, DHX9 is preferentially associated with actively translating polyribosomes and is necessary for efficient translation of RNAs that contain a highly structured 5UTR.
DHX9 might be necessary for maintaining genomic stability as it plays a role in promoting the DNA processing function of WRN. Overexpression of a truncated DHX9 peptide prevents normal BRCA1 function, such as BRCA1 association with nuclear foci following DNA damage. DHX9 associates with gH2AX after DNA damage, suggesting a role for DHX9 in DNA repair.
DHX9 is also necessary for early embryonic development in mice.
Homology
Sequence analysis revealed that DHX9 contains seven helicase core motifs that are conserved among the DEX[D/H] helicase superfamily. DHX9 is highly conserved among man, cow, mouse, worm, and fruit fly.
Mutations
Note
DHX9 truncating mutations were reported to affect the interaction with BRCA1 and RNA polymerase II, and to result in decreased transcriptional activity of BRCA1.
In mammals, DHX9-knockout mice are embryonic lethal for homozygous DHX9 mutants. DHX9 is thus necessary for early embryonic development in mice. It was also suggested that DHX9 is required for the survival and differentiation of embryonic ectoderm.
DHX9 maps to chromosome 1q25 near a major susceptibility locus for prostate cancer.
In mammals, DHX9-knockout mice are embryonic lethal for homozygous DHX9 mutants. DHX9 is thus necessary for early embryonic development in mice. It was also suggested that DHX9 is required for the survival and differentiation of embryonic ectoderm.
DHX9 maps to chromosome 1q25 near a major susceptibility locus for prostate cancer.
Implicated in
Entity name
Lung cancer
Note
DHX9 is over-expressed in tumor samples compared to normal lung tissues. There was a tendency for higher expression levels in small cell lung cancer compared to non-small cell carcinomas.
Prognosis
There was no correlation with tumor stage and survival.
Entity name
Breast cancer
Note
Involvement of DHX9 in breast cancer susceptibility was analyzed in a cohort of breast cancer individuals from non-BRCA1/BRCA2 French Canadian families. This study did not identify any deleterious truncating mutation or aberrant splicing in the DHX9 gene. It was concluded that studies on much bigger cohorts are needed to fully evaluate the association of variants identified with breast cancer risk.
Entity name
Systemic lupus erythematosus (SLE)
Note
Anti-DHX9 is a new serologic marker for SLE. The production of anti-DHX9 may depend on a process restricted to early SLE, or it may be highly sensitive to treatment.
Disease
Systemic lupus erythematosus (SLE) is a largely genetically based disease in which environmental factors are also involved. SLE is an autoimmune disease characterized by autoantibody production and involvement of multiple organ systems. Variable manifestations and outcome reflect the clinical heterogeneity of the disease. It is characterized by acute and chronic inflammation of various tissues of the body including joints, kidneys, mucous membranes, and blood vessel walls.
Prognosis
Among patients with SLE, anti-DHX9 was common in young patients and at an early stage of the disease.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 12851713 | 2003 | Aromatic residues are required for RNA helicase A mediated transactivation. | Aratani S et al |
| 16375861 | 2006 | The nuclear import of RNA helicase A is mediated by importin-alpha3. | Aratani S et al |
| 15312759 | 2004 | A functional interaction between RHA and Ubc9, an E2-like enzyme specific for Sumo-1. | Argasinska J et al |
| 15995249 | 2005 | Nuclear DNA helicase II (RNA helicase A) interacts with Werner syndrome helicase and stimulates its exonuclease activity. | Friedemann J et al |
| 11096080 | 2001 | A Role of RNA Helicase A in cis-Acting Transactivation Response Element-mediated Transcriptional Regulation of Human Immunodeficiency Virus Type 1. | Fujii R et al |
| 19197335 | 2009 | Genetic sequence variations of BRCA1-interacting genes AURKA, BAP1, BARD1 and DHX9 in French Canadian families with high risk of breast cancer. | Guénard F et al |
| 16680162 | 2006 | RNA helicase A is necessary for translation of selected messenger RNAs. | Hartman TR et al |
| 17251188 | 2007 | ZIC2-dependent transcriptional regulation is mediated by DNA-dependent protein kinase, poly(ADP-ribose) polymerase, and RNA helicase A. | Ishiguro A et al |
| 10925702 | 1999 | The human RNA helicase A (DDX9) gene maps to the prostate cancer susceptibility locus at chromosome band 1q25 and its pseudogene (DDX9P) to 13q22, respectively. | Lee CG et al |
| 18519039 | 2008 | The p53 target protein Wig-1 binds hnRNP A2/B1 and RNA Helicase A via RNA. | Prahl M et al |
| 17531811 | 2007 | RNA helicase A interacts with RISC in human cells and functions in RISC loading. | Robb GB et al |
| 16527808 | 2006 | Association of RNA helicase a with human immunodeficiency virus type 1 particles. | Roy BB et al |
| 12592385 | 2003 | Overexpression of a protein fragment of RNA helicase A causes inhibition of endogenous BRCA1 function and defects in ploidy and cytokinesis in mammary epithelial cells. | Schlegel BP et al |
| 10924507 | 2000 | Specific interaction between RNA helicase A and Tap, two cellular proteins that bind to the constitutive transport element of type D retrovirus. | Tang H et al |
| 15355351 | 2004 | RNA helicase A interacts with nuclear factor kappaB p65 and functions as a transcriptional coactivator. | Tetsuka T et al |
| 16740692 | 2006 | Oncoprotein EWS-FLI1 activity is enhanced by RNA helicase A. | Toretsky JA et al |
| 16914450 | 2006 | Characterization of RNA helicase A as component of STAT6-dependent enhanceosome. | Välineva T et al |
| 14654934 | 2004 | Analysis of the RNA helicase A gene in human lung cancer. | Wei X et al |
| 10748171 | 2000 | A novel shuttle protein binds to RNA helicase A and activates the retroviral constitutive transport element. | Westberg C et al |
| 11402034 | 2001 | Mapping the functional domains of HAP95, a protein that binds RNA helicase A and activates the constitutive transport element of type D retroviruses. | Yang JP et al |
| 11687588 | 2002 | Nuclear DNA helicase II/RNA helicase A binds to filamentous actin. | Zhang S et al |
| 15202501 | 2004 | Multiple functions of nuclear DNA helicase II (RNA helicase A) in nucleic acid metabolism. | Zhang S et al |
| 10413677 | 1999 | Nucleolar localization of murine nuclear DNA helicase II (RNA helicase A). | Zhang S et al |
| 14729462 | 2004 | Nuclear DNA helicase II (RNA helicase A) binds to an F-actin containing shell that surrounds the nucleolus. | Zhang S et al |
| 14704337 | 2004 | DNA-dependent protein kinase (DNA-PK) phosphorylates nuclear DNA helicase II/RNA helicase A and hnRNP proteins in an RNA-dependent manner. | Zhang S et al |
| 14769796 | 2004 | RNA helicase A in the MEF1 transcription factor complex up-regulates the MDR1 gene in multidrug-resistant cancer cells. | Zhong X et al |
| 12711669 | 2003 | RNA helicase A interacts with dsDNA and topoisomerase IIalpha. | Zhou K et al |
Other Information
Locus ID:
NCBI: 1660
MIM: 603115
HGNC: 2750
Ensembl: ENSG00000135829
Variants:
dbSNP: 1660
ClinVar: 1660
TCGA: ENSG00000135829
COSMIC: DHX9
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000135829 | ENST00000367549 | Q08211 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37930853 | 2024 | ATR phosphorylates DHX9 at serine 321 to suppress R-loop accumulation upon genotoxic stress. | 4 |
| 38017132 | 2024 | The DNA/RNA helicase DHX9 orchestrates the KDM2B-mediated transcriptional regulation of YAP1 in Ewing sarcoma. | 0 |
| 38110032 | 2024 | Complex interplay between FMRP and DHX9 during DNA replication stress. | 0 |
| 38241710 | 2024 | AKT1 interacts with DHX9 to Mitigate R Loop-Induced Replication Stress in Ovarian Cancer. | 2 |
| 38530197 | 2024 | Induction of Viral Mimicry Upon Loss of DHX9 and ADAR1 in Breast Cancer Cells. | 2 |
| 38594251 | 2024 | DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells. | 0 |
| 37930853 | 2024 | ATR phosphorylates DHX9 at serine 321 to suppress R-loop accumulation upon genotoxic stress. | 4 |
| 38017132 | 2024 | The DNA/RNA helicase DHX9 orchestrates the KDM2B-mediated transcriptional regulation of YAP1 in Ewing sarcoma. | 0 |
| 38110032 | 2024 | Complex interplay between FMRP and DHX9 during DNA replication stress. | 0 |
| 38241710 | 2024 | AKT1 interacts with DHX9 to Mitigate R Loop-Induced Replication Stress in Ovarian Cancer. | 2 |
| 38530197 | 2024 | Induction of Viral Mimicry Upon Loss of DHX9 and ADAR1 in Breast Cancer Cells. | 2 |
| 38594251 | 2024 | DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells. | 0 |
| 36377508 | 2023 | RNA-binding protein DHX9 promotes glioma growth and tumor-associated macrophages infiltration via TCF12. | 13 |
| 37285751 | 2023 | The DHX9 helicase interacts with human DNA polymerase δ4 and stimulates its activity in D-loop extension synthesis. | 0 |
| 37326773 | 2023 | DHX9 Strengthens Atherosclerosis Progression By Promoting Inflammation in Macrophages. | 1 |
Citation
Frédéric Guénard ; Francine Durocher
DHX9 (DEAH (Asp-Glu-Ala-His) box polypeptide 9)
Atlas Genet Cytogenet Oncol Haematol. 2009-07-01
Online version: http://atlasgeneticsoncology.org/gene/44879/dhx9-(deah-(asp-glu-ala-his)-box-polypeptide-9)
