RNA Helicase A

ATP-dependent RNA helicase A (RHA; also known as DHX9, LKP, and NDHI) is an enzyme that in humans is encoded by the DHX9 gene.[5][6][7]

DHX9
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3LLM, 3VYX, 3VYY
Identifiers
Aliases	DHX9, DDX9, LKP, NDH2, NDHII, RHA, RNA Helicase A, DEAH-box helicase 9, DExH-box helicase 9
External IDs	OMIM: 603115 MGI: 108177 HomoloGene: 1039 GeneCards: DHX9
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q25.3 Start 182,839,347 bp[1] End 182,887,982 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1 G3|1 65.37 cM Start 153,455,758 bp[2] End 153,487,660 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • RNA helicase activity • nucleotide binding • GO:0008026 helicase activity • RNA polymerase II transcription factor binding • GO:0001948 protein binding • nucleic acid binding • hydrolase activity • RNA binding • DNA binding • single-stranded DNA binding • double-stranded RNA binding • single-stranded RNA binding • nucleoside-triphosphatase activity • chromatin DNA binding • GO:0033681 3'-5' DNA/RNA helicase activity • GO:0034459 3'-5' RNA helicase activity • triplex DNA binding • nucleoside-triphosphate diphosphatase activity • importin-alpha family protein binding • single-stranded DNA-dependent ATP-dependent 3'-5' DNA helicase activity • siRNA binding • mRNA binding • RNA stem-loop binding • polysome binding • promoter-specific chromatin binding • RNA polymerase II core binding • regulatory region RNA binding • GO:0001104 transcription cofactor activity • GO:0001105 transcription coactivator activity • DNA replication origin binding • double-stranded DNA binding • GO:0004003 DNA helicase activity • ATP binding • ATPase activity • RNA polymerase binding • GO:0043140 3'-5' DNA helicase activity • RISC complex binding • sequence-specific mRNA binding • metal ion binding • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding Cellular component • CRD-mediated mRNA stability complex • cytosol • centrosome • membrane • cytoplasmic ribonucleoprotein granule • cell nucleus • nucleolus • perichromatin fibrils • cytoplasm • nuclear stress granule • nuclear body • polysomal ribosome • polysome • actin cytoskeleton • RISC-loading complex • nucleoplasm • microtubule organizing center • cytoskeleton • macromolecular complex • ribonucleoprotein Biological process • CRD-mediated mRNA stabilization • mRNA splicing, via spliceosome • RNA processing • rhythmic process • protein localization to cytoplasmic stress granule • osteoblast differentiation • positive regulation of type I interferon production • RNA secondary structure unwinding • positive regulation of DNA repair • positive regulation of interferon-beta secretion • positive regulation of transcription from RNA polymerase II promoter • positive regulation of response to cytokine stimulus • cellular response to exogenous dsRNA • positive regulation of interferon-alpha secretion • positive regulation of tumor necrosis factor secretion • positive regulation of interleukin-6 secretion • alternative mRNA splicing, via spliceosome • DNA-templated viral transcription • positive regulation of viral transcription • positive regulation of viral translation • positive regulation of cytoplasmic translation • regulation of transcription from RNA polymerase II promoter • DNA duplex unwinding • positive regulation of DNA replication • positive regulation of fibroblast proliferation • regulation of mRNA processing • positive regulation of NF-kappaB transcription factor activity • cellular response to tumor necrosis factor • positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity • regulation of cytoplasmic translation • targeting of mRNA for destruction involved in RNA interference • positive regulation of interleukin-18 production • G-quadruplex DNA unwinding • positive regulation of innate immune response • positive regulation of RNA export from nucleus • regulation of defense response to virus by host • positive regulation of inflammatory response • pyroptosis • small RNA loading onto RISC • positive regulation of polysome binding • positive regulation of gene silencing by miRNA • immune system process • DNA replication • transcription, DNA-templated • DNA-templated transcription, termination • regulation of transcription, DNA-templated • mRNA processing • regulation of translation • transport • inflammatory response • RNA splicing • gene silencing by RNA • innate immune system • mRNA transport Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1660	13211
Ensembl	ENSG00000135829	ENSMUSG00000042699
UniProt	Q08211	O70133
RefSeq (mRNA)	NM_001357 NM_030588	NM_007842
RefSeq (protein)	NP_001348	NP_031868
Location (UCSC)	Chr 1: 182.84 – 182.89 Mb	Chr 1: 153.46 – 153.49 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

DEAD/DEAH box helicases are proteins, and are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein with RNA helicase activity. It may participate in melting of DNA:RNA hybrids, such as those that occur during transcription, and may play a role in X-linked gene expression. It contains 2 copies of a double-stranded RNA-binding domain, a DEXH core domain and an RGG box. The RNA-binding domains and RGG box influence and regulate RNA helicase activity.[7]The DHX9 gene is located on the long arm q of chromosome 1.

Interactions

DHX9 has been shown to interact with:

• AKAP8L,[8][9]
• BRCA1,[10][11]
• DDX17 (p72)[12]
• DDX5 (p68),
• KHDRBS1,[13]
• MIZF,[14]
• NXF1,[15]
• PRMT1,[16]
• RELA,[17] and
• SMN1.[18]

References

1. GRCh38: Ensembl release 89: ENSG00000135829 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000042699 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Lee CG, Hurwitz J (Aug 1993). "Human RNA helicase A is homologous to the maleless protein of Drosophila". The Journal of Biological Chemistry. 268 (22): 16822–30. PMID 8344961.
6. Zhang S, Grosse F (Apr 1997). "Domain structure of human nuclear DNA helicase II (RNA helicase A)". The Journal of Biological Chemistry. 272 (17): 11487–94. doi:10.1074/jbc.272.17.11487. PMID 9111062.
7. "Entrez Gene: DHX9 DEAH (Asp-Glu-Ala-His) box polypeptide 9".
8. Yang JP, Tang H, Reddy TR, Wong-Staal F (Aug 2001). "Mapping the functional domains of HAP95, a protein that binds RNA helicase A and activates the constitutive transport element of type D retroviruses". The Journal of Biological Chemistry. 276 (33): 30694–700. doi:10.1074/jbc.M102809200. PMID 11402034.
9. Westberg C, Yang JP, Tang H, Reddy TR, Wong-Staal F (Jul 2000). "A novel shuttle protein binds to RNA helicase A and activates the retroviral constitutive transport element". The Journal of Biological Chemistry. 275 (28): 21396–401. doi:10.1074/jbc.M909887199. PMID 10748171.
10. Schlegel BP, Starita LM, Parvin JD (Feb 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". Oncogene. 22 (7): 983–91. doi:10.1038/sj.onc.1206195. PMID 12592385.
11. Anderson SF, Schlegel BP, Nakajima T, Wolpin ES, Parvin JD (Jul 1998). "BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A". Nature Genetics. 19 (3): 254–6. doi:10.1038/930. PMID 9662397.
12. Wilson BJ, Giguère V (November 2007). "Identification of novel pathway partners of p68 and p72 RNA helicases through Oncomine meta-analysis". BMC Genomics. 8: 419. doi:10.1186/1471-2164-8-419. PMC 3225811. PMID 18005418.
13. Reddy TR, Tang H, Xu W, Wong-Staal F (Jul 2000). "Sam68, RNA helicase A and Tap cooperate in the post-transcriptional regulation of human immunodeficiency virus and type D retroviral mRNA". Oncogene. 19 (32): 3570–5. doi:10.1038/sj.onc.1203676. PMID 10951562.
14. Fujita H, Fujii R, Aratani S, Amano T, Fukamizu A, Nakajima T (Apr 2003). "Antithetic effects of MBD2a on gene regulation". Molecular and Cellular Biology. 23 (8): 2645–57. doi:10.1128/mcb.23.8.2645-2657.2003. PMC 152551. PMID 12665568.
15. Tang H, Wong-Staal F (Oct 2000). "Specific interaction between RNA helicase A and Tap, two cellular proteins that bind to the constitutive transport element of type D retrovirus". The Journal of Biological Chemistry. 275 (42): 32694–700. doi:10.1074/jbc.M003933200. PMID 10924507.
16. Smith WA, Schurter BT, Wong-Staal F, David M (May 2004). "Arginine methylation of RNA helicase a determines its subcellular localization". The Journal of Biological Chemistry. 279 (22): 22795–8. doi:10.1074/jbc.C300512200. PMID 15084609.
17. Tetsuka T, Uranishi H, Sanda T, Asamitsu K, Yang JP, Wong-Staal F, Okamoto T (Sep 2004). "RNA helicase A interacts with nuclear factor kappaB p65 and functions as a transcriptional coactivator". European Journal of Biochemistry / FEBS. 271 (18): 3741–51. doi:10.1111/j.1432-1033.2004.04314.x. PMID 15355351.
18. Pellizzoni L, Charroux B, Rappsilber J, Mann M, Dreyfuss G (Jan 2001). "A functional interaction between the survival motor neuron complex and RNA polymerase II". The Journal of Cell Biology. 152 (1): 75–85. doi:10.1083/jcb.152.1.75. PMC 2193649. PMID 11149922.

Further reading

• Lee CG, Hurwitz J (Mar 1992). "A new RNA helicase isolated from HeLa cells that catalytically translocates in the 3' to 5' direction". The Journal of Biological Chemistry. 267 (7): 4398–407. PMID 1537828.
• Lee CG, Zamore PD, Green MR, Hurwitz J (Jun 1993). "RNA annealing activity is intrinsically associated with U2AF". The Journal of Biological Chemistry. 268 (18): 13472–8. PMID 7685763.
• Abdelhaleem MM, Hameed S, Klassen D, Greenberg AH (Mar 1996). "Leukophysin: an RNA helicase A-related molecule identified in cytotoxic T cell granules and vesicles". Journal of Immunology. 156 (6): 2026–35. PMID 8690889.
• Nakajima T, Uchida C, Anderson SF, Lee CG, Hurwitz J, Parvin JD, Montminy M (Sep 1997). "RNA helicase A mediates association of CBP with RNA polymerase II". Cell. 90 (6): 1107–12. doi:10.1016/S0092-8674(00)80376-1. PMID 9323138.
• Loor G, Zhang SJ, Zhang P, Toomey NL, Lee MY (Dec 1997). "Identification of DNA replication and cell cycle proteins that interact with PCNA". Nucleic Acids Research. 25 (24): 5041–6. doi:10.1093/nar/25.24.5041. PMC 147130. PMID 9396813.
• Lee CG, Eki T, Okumura K, da Costa Soares V, Hurwitz J (Feb 1998). "Molecular analysis of the cDNA and genomic DNA encoding mouse RNA helicase A". Genomics. 47 (3): 365–71. doi:10.1006/geno.1997.5139. PMID 9480750.
• Anderson SF, Schlegel BP, Nakajima T, Wolpin ES, Parvin JD (Jul 1998). "BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A". Nature Genetics. 19 (3): 254–6. doi:10.1038/930. PMID 9662397.
• Lee CG, da Costa Soares V, Newberger C, Manova K, Lacy E, Hurwitz J (Nov 1998). "RNA helicase A is essential for normal gastrulation". Proceedings of the National Academy of Sciences of the United States of America. 95 (23): 13709–13. doi:10.1073/pnas.95.23.13709. PMC 24884. PMID 9811865.
• Li J, Tang H, Mullen TM, Westberg C, Reddy TR, Rose DW, Wong-Staal F (Jan 1999). "A role for RNA helicase A in post-transcriptional regulation of HIV type 1". Proceedings of the National Academy of Sciences of the United States of America. 96 (2): 709–14. doi:10.1073/pnas.96.2.709. PMC 15201. PMID 9892698.
• Tang H, McDonald D, Middlesworth T, Hope TJ, Wong-Staal F (May 1999). "The carboxyl terminus of RNA helicase A contains a bidirectional nuclear transport domain". Molecular and Cellular Biology. 19 (5): 3540–50. doi:10.1128/mcb.19.5.3540. PMC 84146. PMID 10207077.
• Westberg C, Yang JP, Tang H, Reddy TR, Wong-Staal F (Jul 2000). "A novel shuttle protein binds to RNA helicase A and activates the retroviral constitutive transport element". The Journal of Biological Chemistry. 275 (28): 21396–401. doi:10.1074/jbc.M909887199. PMID 10748171.
• Tang H, Wong-Staal F (Oct 2000). "Specific interaction between RNA helicase A and Tap, two cellular proteins that bind to the constitutive transport element of type D retrovirus". The Journal of Biological Chemistry. 275 (42): 32694–700. doi:10.1074/jbc.M003933200. PMID 10924507.
• Lee CG, Eki T, Okumura K, Nogami M, Soares Vda C, Murakami Y, Hanaoka F, Hurwitz J (Jan 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". Somatic Cell and Molecular Genetics. 25 (1): 33–9. doi:10.1023/B:SCAM.0000007138.44216.3a. PMID 10925702.
• Reddy TR, Tang H, Xu W, Wong-Staal F (Jul 2000). "Sam68, RNA helicase A and Tap cooperate in the post-transcriptional regulation of human immunodeficiency virus and type D retroviral mRNA". Oncogene. 19 (32): 3570–5. doi:10.1038/sj.onc.1203676. PMID 10951562.
• Pellizzoni L, Charroux B, Rappsilber J, Mann M, Dreyfuss G (Jan 2001). "A functional interaction between the survival motor neuron complex and RNA polymerase II". The Journal of Cell Biology. 152 (1): 75–85. doi:10.1083/jcb.152.1.75. PMC 2193649. PMID 11149922.
• Takasaki Y, Kogure T, Takeuchi K, Kaneda K, Yano T, Hirokawa K, Hirose S, Shirai T, Hashimoto H (Apr 2001). "Reactivity of anti-proliferating cell nuclear antigen (PCNA) murine monoclonal antibodies and human autoantibodies to the PCNA multiprotein complexes involved in cell proliferation". Journal of Immunology. 166 (7): 4780–7. doi:10.4049/jimmunol.166.7.4780. PMID 11254741.
• Yang JP, Tang H, Reddy TR, Wong-Staal F (Aug 2001). "Mapping the functional domains of HAP95, a protein that binds RNA helicase A and activates the constitutive transport element of type D retroviruses". The Journal of Biological Chemistry. 276 (33): 30694–700. doi:10.1074/jbc.M102809200. PMID 11402034.
• Aratani S, Fujii R, Oishi T, Fujita H, Amano T, Ohshima T, Hagiwara M, Fukamizu A, Nakajima T (Jul 2001). "Dual roles of RNA helicase A in CREB-dependent transcription". Molecular and Cellular Biology. 21 (14): 4460–9. doi:10.1128/MCB.21.14.4460-4469.2001. PMC 87106. PMID 11416126.