ADAR
For other uses, see Adar (disambiguation).
Double-stranded RNA-specific adenosine deaminase is an enzyme that in humans is encoded by the ADAR gene (which stands for adenosine deaminase acting on RNA).[1][2]
This gene encodes the enzyme responsible for RNA editing by site-specific deamination of adenosines. This enzyme destabilizes double stranded RNA through conversion of adenosine to inosine. ADAR protein is a RNA-binding protein, which functions in RNA-editing through post-transcriptional modification of mRNA transcripts by changing the nucleotide content of the RNA. Mutations in this gene have been associated with dyschromatosis symmetrica hereditaria, as well as Aicardi–Goutières syndrome.[3] Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[2]
Model organisms
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Abnormal |
| Recessive lethal study | Abnormal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Plasma immunoglobulins | Normal |
| Haematology | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Skin Histopathology | Normal |
| Brain histopathology | Normal |
| Salmonella infection | Normal[4] |
| Citrobacter infection | Normal[5] |
| All tests and analysis from[6][7] |
Model organisms have been used in the study of ADAR function. A conditional knockout mouse line, called Adartm1a(EUCOMM)Wtsi[8][9] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[10][11][12]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[6][13] Twenty five tests were carried out on mutant mice and two significant abnormalities were observed.[6] Few homozygous mutant embryos were identified during gestation, and none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and no abnormalities were observed in these animals.[6]
See also
References
- ↑ Kim U, Wang Y, Sanford T, Zeng Y, Nishikura K (Dec 1994). "Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing". Proc Natl Acad Sci USA 91 (24): 11457–61. doi:10.1073/pnas.91.24.11457. PMC 45250. PMID 7972084.
- ↑ 2.0 2.1 "Entrez Gene: ADAR Adenosine Deaminase Acting on RNA".
- ↑ Rice, GI et al. (November 2012). "Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature.". Nature Genetics 44 (11): 1243–8. doi:10.1038/ng.2414. PMID 23001123.
- ↑ "Salmonella infection data for Adar". Wellcome Trust Sanger Institute.
- ↑ "Citrobacter infection data for Adar". Wellcome Trust Sanger Institute.
- ↑ 6.0 6.1 6.2 6.3 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
- ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ↑ "International Knockout Mouse Consortium".
- ↑ "Mouse Genome Informatics".
- ↑ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
- ↑ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ↑ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
Further reading
- Valenzuela A, Blanco J, Callebaut C et al. (1997). "HIV-1 envelope gp120 and viral particles block adenosine deaminase binding to human CD26". Adv. Exp. Med. Biol. 421: 185–92. doi:10.1007/978-1-4757-9613-1_24. PMID 9330696.
- Wathelet MG, Szpirer J, Nols CB et al. (1988). "Cloning and chromosomal location of human genes inducible by type I interferon". Somat. Cell Mol. Genet. 14 (5): 415–26. doi:10.1007/BF01534709. PMID 3175763.
- Wang Y, Zeng Y, Murray JM, Nishikura K (1996). "Genomic organization and chromosomal location of the human dsRNA adenosine deaminase gene: the enzyme for glutamate-activated ion channel RNA editing". J. Mol. Biol. 254 (2): 184–95. doi:10.1006/jmbi.1995.0610. PMID 7490742.
- Patterson JB, Samuel CE (1995). "Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase". Mol. Cell. Biol. 15 (10): 5376–88. PMC 230787. PMID 7565688.
- Patterson JB, Thomis DC, Hans SL, Samuel CE (1995). "Mechanism of interferon action: double-stranded RNA-specific adenosine deaminase from human cells is inducible by alpha and gamma interferons". Virology 210 (2): 508–11. doi:10.1006/viro.1995.1370. PMID 7618288.
- O'Connell MA, Krause S, Higuchi M et al. (1995). "Cloning of cDNAs encoding mammalian double-stranded RNA-specific adenosine deaminase". Mol. Cell. Biol. 15 (3): 1389–97. PMC 230363. PMID 7862132.
- Weier HU, George CX, Greulich KM, Samuel CE (1996). "The interferon-inducible, double-stranded RNA-specific adenosine deaminase gene (DSRAD) maps to human chromosome 1q21.1-21.2". Genomics 30 (2): 372–5. doi:10.1006/geno.1995.0034. PMID 8586444.
- Liu Y, George CX, Patterson JB, Samuel CE (1997). "Functionally distinct double-stranded RNA-binding domains associated with alternative splice site variants of the interferon-inducible double-stranded RNA-specific adenosine deaminase". J. Biol. Chem. 272 (7): 4419–28. doi:10.1074/jbc.272.7.4419. PMID 9020165.
- Valenzuela A, Blanco J, Callebaut C et al. (1997). "Adenosine deaminase binding to human CD26 is inhibited by HIV-1 envelope glycoprotein gp120 and viral particles". J. Immunol. 158 (8): 3721–9. PMID 9103436.
- Herbert A, Alfken J, Kim YG et al. (1997). "A Z-DNA binding domain present in the human editing enzyme, double-stranded RNA adenosine deaminase". Proc. Natl. Acad. Sci. U.S.A. 94 (16): 8421–6. doi:10.1073/pnas.94.16.8421. PMC 22942. PMID 9237992.
- Liu Y, Herbert A, Rich A, Samuel CE (1998). "Double-stranded RNA-specific adenosine deaminase: nucleic acid binding properties". Methods 15 (3): 199–205. doi:10.1006/meth.1998.0624. PMID 9735305.
- George CX, Samuel CE (1999). "Human RNA-specific adenosine deaminase ADAR1 transcripts possess alternative exon 1 structures that initiate from different promoters, one constitutively active and the other interferon inducible". Proc. Natl. Acad. Sci. U.S.A. 96 (8): 4621–6. doi:10.1073/pnas.96.8.4621. PMC 16382. PMID 10200312.
- Schwartz T, Rould MA, Lowenhaupt K et al. (1999). "Crystal structure of the Zalpha domain of the human editing enzyme ADAR1 bound to left-handed Z-DNA". Science 284 (5421): 1841–5. doi:10.1126/science.284.5421.1841. PMID 10364558.
- Schade M, Turner CJ, Kühne R et al. (1999). "The solution structure of the Zα domain of the human RNA editing enzyme ADAR1 reveals a prepositioned binding surface for Z-DNA". Proc. Natl. Acad. Sci. U.S.A. 96 (22): 12465–70. doi:10.1073/pnas.96.22.12465. PMC 22950. PMID 10535945.
- Blanco J, Valenzuela A, Herrera C et al. (2000). "The HIV-1 gp120 inhibits the binding of adenosine deaminase to CD26 by a mechanism modulated by CD4 and CXCR4 expression". FEBS Lett. 477 (1–2): 123–8. doi:10.1016/S0014-5793(00)01751-8. PMID 10899322.
- Herrera C, Morimoto C, Blanco J et al. (2001). "Comodulation of CXCR4 and CD26 in human lymphocytes". J. Biol. Chem. 276 (22): 19532–9. doi:10.1074/jbc.M004586200. PMID 11278278.
- Wong SK, Sato S, Lazinski DW (2001). "Substrate recognition by ADAR1 and ADAR2". RNA 7 (6): 846–58. doi:10.1017/S135583820101007X. PMC 1370134. PMID 11421361.
- Eckmann CR, Neunteufl A, Pfaffstetter L, Jantsch MF (2001). "The Human But Not the Xenopus RNA-editing Enzyme ADAR1 Has an Atypical Nuclear Localization Signal and Displays the Characteristics of a Shuttling Protein". Mol. Biol. Cell 12 (7): 1911–24. doi:10.1091/mbc.12.7.1911. PMC 55639. PMID 11451992.
External links
- OMIM entries on Dyschromatosis Symmetrica Hereditaria 1
- ADAR human gene location in the UCSC Genome Browser.
- ADAR human gene details in the UCSC Genome Browser.
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