DDX5 explained

Probable ATP-dependent RNA helicase DDX5 also known as DEAD box protein 5 or RNA helicase p68 is an enzyme that in humans is encoded by the DDX5 gene.^[1]

Function

DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), 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,^[2] and cellular growth and division. This gene encodes a DEAD box protein, which is an RNA-dependent ATPase, and also a proliferation-associated nuclear antigen, specifically reacting with the simian virus 40 tumor antigen. This gene consists of 13 exons, and alternatively spliced transcripts containing several intron sequences have been detected, but no isoforms encoded by these transcripts have been identified.

Interactions

DDX5 has been shown to interact with:

• AKAP8,^[3]
• DDX17 (p72),^[4]
• DHX9 (RNA helicase A),^[5]
• Estrogen receptor alpha,^[6]
• Fibrillarin,^[7]
• HDAC1,^[8]
• p53,^[9]
• CTCF.^[10]

Further reading

• Iggo RD, Jamieson DJ, MacNeill SA . p68 RNA helicase: identification of a nucleolar form and cloning of related genes containing a conserved intron in yeasts . Mol. Cell. Biol. . 11 . 3 . 1326–33 . 1991 . 1996094 . 10.1128/MCB.11.3.1326. 369403 . etal.
• Hloch P, Schiedner G, Stahl H . Complete cDNA sequence of the human p68 protein . Nucleic Acids Res. . 18 . 10 . 3045 . 1990 . 2349099 . 10.1093/nar/18.10.3045 . 330836 .
• Ford MJ, Anton IA, Lane DP . Nuclear protein with sequence homology to translation initiation factor eIF-4A . Nature . 332 . 6166 . 736–8 . 1988 . 2451786 . 10.1038/332736a0 . 1988Natur.332..736F . 4351448 .
• Iggo R, Gough A, Xu W . Chromosome mapping of the human gene encoding the 68-kDa nuclear antigen (p68) by using the polymerase chain reaction . Proc. Natl. Acad. Sci. U.S.A. . 86 . 16 . 6211–4 . 1989 . 2762324 . 10.1073/pnas.86.16.6211 . 297807 . 1989PNAS...86.6211I . etal. free .
• Buelt MK, Glidden BJ, Storm DR . Regulation of p68 RNA helicase by calmodulin and protein kinase C . J. Biol. Chem. . 269 . 47 . 29367–70 . 1994 . 10.1016/S0021-9258(18)43885-9 . 7525583 . free .
• Brody LC, Abel KJ, Castilla LH . Construction of a transcription map surrounding the BRCA1 locus of human chromosome 17 . Genomics . 25 . 1 . 238–47 . 1995 . 7774924 . 10.1016/0888-7543(95)80131-5 . etal. free .
• Rössler OG, Hloch P, Schütz N . Structure and expression of the human p68 RNA helicase gene . Nucleic Acids Res. . 28 . 4 . 932–9 . 2000 . 10648785 . 10.1093/nar/28.4.932 . 102575 . etal.
• Nicol SM, Causevic M, Prescott AR, Fuller-Pace FV . The nuclear DEAD box RNA helicase p68 interacts with the nucleolar protein fibrillarin and colocalizes specifically in nascent nucleoli during telophase . Exp. Cell Res. . 257 . 2 . 272–80 . 2000 . 10837141 . 10.1006/excr.2000.4886 .
• Akileswaran L, Taraska JW, Sayer JA . A-kinase-anchoring protein AKAP95 is targeted to the nuclear matrix and associates with p68 RNA helicase . J. Biol. Chem. . 276 . 20 . 17448–54 . 2001 . 11279182 . 10.1074/jbc.M101171200 . etal. free .
• Andersen JS, Lyon CE, Fox AH . Directed proteomic analysis of the human nucleolus . Curr. Biol. . 12 . 1 . 1–11 . 2002 . 11790298 . 10.1016/S0960-9822(01)00650-9 . 14132033 . etal. free . 2002CBio...12....1A .
• Jurica MS, Licklider LJ, Gygi SR . Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis . RNA . 8 . 4 . 426–39 . 2002 . 11991638 . 10.1017/S1355838202021088 . 1370266 . etal.
• Liu ZR . p68 RNA Helicase Is an Essential Human Splicing Factor That Acts at the U1 snRNA-5′ Splice Site Duplex . Mol. Cell. Biol. . 22 . 15 . 5443–50 . 2002 . 12101238 . 10.1128/MCB.22.15.5443-5450.2002 . 133941 .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Rossow KL, Janknecht R . Synergism between p68 RNA helicase and the transcriptional coactivators CBP and p300 . Oncogene . 22 . 1 . 151–6 . 2003 . 12527917 . 10.1038/sj.onc.1206067 . free .
• Guil S, Gattoni R, Carrascal M . Roles of hnRNP A1, SR Proteins, and p68 Helicase in c-H-ras Alternative Splicing Regulation . Mol. Cell. Biol. . 23 . 8 . 2927–41 . 2003 . 12665590 . 10.1128/MCB.23.8.2927-2941.2003 . 152554 . etal.
• Fujita T, Kobayashi Y, Wada O . Full activation of estrogen receptor alpha activation function-1 induces proliferation of breast cancer cells . J. Biol. Chem. . 278 . 29 . 26704–14 . 2003 . 12738788 . 10.1074/jbc.M301031200 . etal. free .
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .

Notes and References

1. Web site: Entrez Gene: DDX5 DEAD (Asp-Glu-Ala-Asp) box polypeptide 5.
2. Legrand . JMD . Chan . AL . La . HM . Rossello . FJ . Änkö . ML . Fuller-Pace . FV . Hobbs . RM . DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia. . Nature Communications . 23 May 2019 . 10 . 1 . 2278 . 10.1038/s41467-019-09972-7 . 31123254. 6533336 . 2019NatCo..10.2278L .
3. Akileswaran L, Taraska JW, Sayer JA, Gettemy JM, Coghlan VM . A-kinase-anchoring protein AKAP95 is targeted to the nuclear matrix and associates with p68 RNA helicase . J. Biol. Chem. . 276 . 20 . 17448–54 . May 2001 . 11279182 . 10.1074/jbc.M101171200 . free .
4. Ogilvie VC, Wilson BJ, Nicol SM, Morrice NA, Saunders LR, Barber GN, Fuller-Pace FV . The highly related DEAD box RNA helicases p68 and p72 exist as heterodimers in cells . Nucleic Acids Res. . 31 . 5 . 1470–80 . March 2003 . 12595555 . 149829 . 10.1093/nar/gkg236 .
5. Wilson BJ, Giguère V . Identification of novel pathway partners of p68 and p72 RNA helicases through Oncomine meta-analysis . BMC Genomics . 8. 419 . 2007 . 18005418 . 10.1186/1471-2164-8-419 . 3225811 . free .
6. Rossow KL, Janknecht R . Synergism between p68 RNA helicase and the transcriptional coactivators CBP and p300 . Oncogene . 22 . 1 . 151–6 . January 2003 . 12527917 . 10.1038/sj.onc.1206067 . free .
7. Nicol SM, Causevic M, Prescott AR, Fuller-Pace FV . The nuclear DEAD box RNA helicase p68 interacts with the nucleolar protein fibrillarin and colocalizes specifically in nascent nucleoli during telophase . Exp. Cell Res. . 257 . 2 . 272–80 . June 2000 . 10837141 . 10.1006/excr.2000.4886 .
8. Wilson BJ, Bates GJ, Nicol SM, Gregory DJ, Perkins ND, Fuller-Pace FV . The p68 and p72 DEAD box RNA helicases interact with HDAC1 and repress transcription in a promoter-specific manner . BMC Mol. Biol. . 5. 11 . August 2004 . 15298701 . 514542 . 10.1186/1471-2199-5-11 . free .
9. Bates GJ, Nicol SM, Wilson BJ, Jacobs AM, Bourdon JC, Wardrop J, Gregory DJ, Lane DP, Perkins ND, Fuller-Pace FV . The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor . EMBO J. . 24 . 3 . 543–53 . February 2005 . 15660129 . 548656 . 10.1038/sj.emboj.7600550 .
10. Yao H, Brick K, Evrard Y, Xiao T, Camerini-Otero RD, Felsenfeld G . Mediation of CTCF transcriptional insulation by DEAD-box RNA-binding protein p68 and steroid receptor RNA activator SRA . Genes Dev . 24 . 22 . 2543–2555 . 2010 . 20966046 . 2975930. 10.1101/gad.1967810 .