DHX9 (DEAH (Asp-Glu-Ala-His) box polypeptide 9)

2009-07-01   Frédéric Guénard , Francine Durocher 

Cancer Genomics Laboratory, Oncology, Molecular Endocrinology Research Centre, CRCHUL, CHUQ, Laval University, Québec, G1V 4G2, Canada

Identity

HGNC
LOCATION
1q25.3
LOCUSID
ALIAS
DDX9,LKP,NDH2,NDHII,RHA

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

Atlas Image
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.

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.

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.

Bibliography

Pubmed IDLast YearTitleAuthors
128517132003Aromatic residues are required for RNA helicase A mediated transactivation.Aratani S et al
163758612006The nuclear import of RNA helicase A is mediated by importin-alpha3.Aratani S et al
153127592004A functional interaction between RHA and Ubc9, an E2-like enzyme specific for Sumo-1.Argasinska J et al
159952492005Nuclear DNA helicase II (RNA helicase A) interacts with Werner syndrome helicase and stimulates its exonuclease activity.Friedemann J et al
110960802001A Role of RNA Helicase A in cis-Acting Transactivation Response Element-mediated Transcriptional Regulation of Human Immunodeficiency Virus Type 1.Fujii R et al
191973352009Genetic 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
166801622006RNA helicase A is necessary for translation of selected messenger RNAs.Hartman TR et al
172511882007ZIC2-dependent transcriptional regulation is mediated by DNA-dependent protein kinase, poly(ADP-ribose) polymerase, and RNA helicase A.Ishiguro A et al
109257021999The 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
185190392008The p53 target protein Wig-1 binds hnRNP A2/B1 and RNA Helicase A via RNA.Prahl M et al
175318112007RNA helicase A interacts with RISC in human cells and functions in RISC loading.Robb GB et al
165278082006Association of RNA helicase a with human immunodeficiency virus type 1 particles.Roy BB et al
125923852003Overexpression 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
109245072000Specific 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
153553512004RNA helicase A interacts with nuclear factor kappaB p65 and functions as a transcriptional coactivator.Tetsuka T et al
167406922006Oncoprotein EWS-FLI1 activity is enhanced by RNA helicase A.Toretsky JA et al
169144502006Characterization of RNA helicase A as component of STAT6-dependent enhanceosome.Välineva T et al
146549342004Analysis of the RNA helicase A gene in human lung cancer.Wei X et al
107481712000A novel shuttle protein binds to RNA helicase A and activates the retroviral constitutive transport element.Westberg C et al
114020342001Mapping 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
116875882002Nuclear DNA helicase II/RNA helicase A binds to filamentous actin.Zhang S et al
152025012004Multiple functions of nuclear DNA helicase II (RNA helicase A) in nucleic acid metabolism.Zhang S et al
104136771999Nucleolar localization of murine nuclear DNA helicase II (RNA helicase A).Zhang S et al
147294622004Nuclear DNA helicase II (RNA helicase A) binds to an F-actin containing shell that surrounds the nucleolus.Zhang S et al
147043372004DNA-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
147697962004RNA helicase A in the MEF1 transcription factor complex up-regulates the MDR1 gene in multidrug-resistant cancer cells.Zhong X et al
127116692003RNA 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 IDTranscript IDUniprot
ENSG00000135829ENST00000367549Q08211

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
Toll-Like Receptors CascadesREACTOMER-HSA-168898
Toll Like Receptor 10 (TLR10) CascadeREACTOMER-HSA-168142
MyD88 cascade initiated on plasma membraneREACTOMER-HSA-975871
TAK1 activates NFkB by phosphorylation and activation of IKKs complexREACTOMER-HSA-445989
Toll Like Receptor 3 (TLR3) CascadeREACTOMER-HSA-168164
MyD88-independent TLR3/TLR4 cascadeREACTOMER-HSA-166166
TRIF-mediated TLR3/TLR4 signalingREACTOMER-HSA-937061
Toll Like Receptor 5 (TLR5) CascadeREACTOMER-HSA-168176
Toll Like Receptor 7/8 (TLR7/8) CascadeREACTOMER-HSA-168181
MyD88 dependent cascade initiated on endosomeREACTOMER-HSA-975155
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activationREACTOMER-HSA-975138
Toll Like Receptor 9 (TLR9) CascadeREACTOMER-HSA-168138
Toll Like Receptor 4 (TLR4) CascadeREACTOMER-HSA-166016
Activated TLR4 signallingREACTOMER-HSA-166054
MyD88:Mal cascade initiated on plasma membraneREACTOMER-HSA-166058
Toll Like Receptor 2 (TLR2) CascadeREACTOMER-HSA-181438
Toll Like Receptor TLR1:TLR2 CascadeREACTOMER-HSA-168179
Toll Like Receptor TLR6:TLR2 CascadeREACTOMER-HSA-168188
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathwaysREACTOMER-HSA-168928
TRAF6 mediated NF-kB activationREACTOMER-HSA-933542
Cytosolic sensors of pathogen-associated DNAREACTOMER-HSA-1834949
ZBP1(DAI) mediated induction of type I IFNsREACTOMER-HSA-1606322
RIP-mediated NFkB activation via ZBP1REACTOMER-HSA-1810476
DEx/H-box helicases activate type I IFN and inflammatory cytokines productionREACTOMER-HSA-3134963
Gene ExpressionREACTOMER-HSA-74160
Processing of Capped Intron-Containing Pre-mRNAREACTOMER-HSA-72203
mRNA SplicingREACTOMER-HSA-72172
mRNA Splicing - Major PathwayREACTOMER-HSA-72163

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
206968862010Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells.132
283551802017DHX9 suppresses RNA processing defects originating from the Alu invasion of the human genome.91
175318112007RNA helicase A interacts with RISC in human cells and functions in RISC loading.89
215618112011Human DHX9 helicase preferentially unwinds RNA-containing displacement loops (R-loops) and G-quadruplexes.71
219571492011DHX9 pairs with IPS-1 to sense double-stranded RNA in myeloid dendritic cells.64
165278082006Association of RNA helicase a with human immunodeficiency virus type 1 particles.52
208021562010RNA helicase A is a DNA-binding partner for EGFR-mediated transcriptional activation in the nucleus.49
125923852003Overexpression of a protein fragment of RNA helicase A causes inhibition of endogenous BRCA1 function and defects in ploidy and cytokinesis in mammary epithelial cells.40
221907482012A novel role of RNA helicase A in regulation of translation of type I collagen mRNAs.38
297424422018RNA/DNA Hybrid Interactome Identifies DXH9 as a Molecular Player in Transcriptional Termination and R-Loop-Associated DNA Damage.38

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