Disease relevance of DHX9

• Here, we report that NDH II interacts with the Werner syndrome helicase WRN, an enzyme associated with premature aging and predisposition to tumorigenesis [1].
• Here, we report that RHA also plays a role in Rev/RRE-mediated gene expression and HIV replication [2].
• 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 [3].
• Using phage display library screening, we identified an EWS-FLI1 binding peptide containing homology to RHA [4].
• This interaction results in specific incorporation of RHA into HIV-1 particles [5].

Psychiatry related information on DHX9

• Moreover, horizontal, vertical, and total motor activities throughout the 120-min observation period that followed the administration of vehicle tended to be larger in RHA/Verh rats, although the difference between the two lines was not statistically significant [6].
• Consummatory behavior elicited by mild tail pinch in the presence of solid food was studied in male Roman high-avoidance (RHA/Verh) and Roman low-avoidance (RLA/Verh) rats [7].
• Mental health censuses in Mersey RHA [8].
• Clinical decision-making: a study of general surgery within Trent RHA [9].

High impact information on DHX9

• We show here that RNA helicase A (RHA) protein links BRCA1 to the holoenzyme complex [10].
• In transient transfection assays, RHA was found to cooperate with CBP in mediating target gene activation via the CAMP responsive factor CREB [11].
• NDH-2 accomplish the turnover of NAD(P)H, regenerating the NAD(P)(+) pool, and may contribute to the generation of a membrane potential through complexes III and IV [12].
• NDH-2 have particular relevance in yeasts like Saccharomyces cerevisiae and in several prokaryotes, whose respiratory chains are devoid of complex I, in which NDH-2 keep the balance and are the main entry point of electrons into the respiratory chains [12].
• First trimester chromosomal analysis of complex structural rearrangements with RHA banding on chorionic villi [13].

Chemical compound and disease context of DHX9

• In RHA/Verh rats, locomotion, rearing, and total motor activity were significantly more intense after acute cocaine and morphine challenges than after vehicle administration, whereas no significant differences in motor activity were observed between control and cocaine- or morphine-treated RLA/Verh rats [6].

Biological context of DHX9

• Thus, our study demonstrates, for the first time, the involvement of RHA in up-regulation of the MDR1 gene [14].
• Interactions of RHA with other protein factors in the MEF1 complex bound to the promoter element may contribute to P-gp overexpression and multidrug resistance phenotype in drug-resistant cancer cells [14].
• Thereby, the NDH II DEXH domain alone, i.e. its catalytic core, was able to support binding to gamma-H2AX [15].
• Taken together, these results suggest that NDH II plays a role in promoting the DNA processing function of WRN, which in turn might be necessary for maintaining genomic stability [1].
• MBD2a and RHA cooperatively enhanced CREB-dependent gene expression [16].

Anatomical context of DHX9

• Utilizing a previously described interaction between BRCA1 and RNA helicase A (RHA), we have developed a dominant-negative approach to block BRCA1 function in human breast epithelial cells [17].
• An RNA-dependent association of Ku antigen with nuclear DNA helicase II (NDH II), alternatively named RNA helicase A (RHA), was found in nuclear extracts of HeLa cells by immunoprecipitation and by gel filtration chromatography [18].
• We propose that RHA is required to release both CTE- and RRE-containing mRNA from spliceosomes before completion of splicing, thus freeing them for nuclear export [2].
• These observations indicate that RHA is necessary for early embryonic development and suggest the requirement of RHA for the survival and differentiation of embryonic ectoderm [19].
• In addition, we show that nucleolar accumulation of NDH II is closely related to G(0)-phase growth arrest in human fibroblasts [20].

Associations of DHX9 with chemical compounds

• Congruently, after actinomycin D treatment, NDH II accumulated in RNA-containing nuclear bodies that predominantly co-localized with gamma-H2AX foci [15].
• These findings provide evidence for a novel arginine methylation-dependent regulatory pathway controlling the nuclear import of RHA [21].
• Our results suggested that an altered conformation of the A/B region induced by aldosterone, but not hydrocortisone, might determine the accessibility of MR AF-1a to RHA/CBP complexes [22].
• These results indicate that aromatic characteristics of tryptophan residues in MTAD are important for CREB-dependent transcription via RHA [23].
• Type II NAD(P)H:quinone oxidoreductases (NDH-2) catalyze the two-electron transfer from NAD(P)H to quinones, without any energy-transducing site [12].

Physical interactions of DHX9

• RHA binds to Sam68 and to Tap both in vivo and in vitro [24].
• Taken together, these data support the proposal that HAP95 specifically facilitates CTE-mediated gene expression by directly binding to RHA [25].
• The N- and C-termini of RHA bound the E'F loop of the DNA-binding domain of TonEBP [26].

Enzymatic interactions of DHX9

• It was also found that the oxidation of NADPH in the A. vinelandii respiratory chain is catalyzed solely by NDH II [27].

Co-localisations of DHX9

• Immunofluorescence and ultrastructural studies showed that NDH II colocalizes with a small subset of PML NBs in control cells, however, colocalizes with practically all bodies in interferon-alpha-stimulated cells [28].

Regulatory relationships of DHX9

• Furthermore, NDH II enhanced the degradation of D-loop DNA by the WRN exonuclease [1].
• Taken together, these results suggest that histone gamma-H2AX promotes binding of NDH II to transcriptionally stalled sites on chromosomal DNA [15].
• Overexpression of RHA inhibited the activity of TonEBP; however, catalytic activity of RHA was dispensable for the inhibition [26].

Other interactions of DHX9

• On the other hand, the 3' --> 5' exonuclease activity of WRN was increased by the presence of NDH II [1].
• Chromatin immunoprecipitation revealed that RHA occupies the MDR1 promoter in vivo [14].
• Interestingly, coimmunoprecipitation assays demonstrated that MBD2a binding to RHA was not associated with histone deacetylase 1 [16].
• Here, we report for the first time that some NDH II/RNA helicase A is a component of promyelocytic leukemia nuclear bodies (PML NBs) [28].
• An in vivo binding assay revealed that MBD2a selectively interacted with RNA helicase A (RHA), a component of CREB transcriptional coactivator complexes [16].

Analytical, diagnostic and therapeutic context of DHX9

• Western blotting showed that RHA in drug-resistant cells had a higher molecular weight than that in drug-sensitive cells [14].
• The antibody against RHA specifically disrupted the complex formation in electrophoretic mobility shift assay, confirming the identity of RHA [14].
• NDH II was present in the immunoprecipitates as shown by mass spectrometry and by immunoblotting [28].
• The interaction between p65 and RHA was confirmed by glutathione-S transferase pull-down assay in vitro, and by co-immunoprecipitation assay in vivo [29].
• Histological analysis, combined with terminal deoxynucleotidyltransferase-mediated UTP end labeling (TUNEL) reactions of RHA-null embryos, revealed marked apoptotic cell death specifically in embryonic ectodermal cells during gastrulation [19].

References