ADAR

Official Full Name

adenosine deaminase RNA specific

Organism

Homo sapiens

Gene ID

103

Background

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. Mutations in this gene have been associated with dyschromatosis symmetrica hereditaria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

Cat.No.	Product Name	Price
CSC-DC000274	Panoply™ Human ADAR Knockdown Stable Cell Line	Inquiry
CSC-SC000274	Panoply™ Human ADAR Over-expressing Stable Cell Line	Inquiry
CLKO-0958	ADAR KO Cell Lysate-HEK293T	Inquiry
CSC-RT2803	Human ADAR Knockout Cell Line-HEK293	Inquiry

Cat.No.	Product Name	Price
AD00677Z	Human ADAR adenoviral particles	Inquiry
LV00190Z	Human ADAR lentiviral particles	Inquiry
LV00192Z	Human ADAR lentiviral particles	Inquiry
LV00193Z	Human ADAR lentiviral particles	Inquiry
LV00194Z	Human ADAR lentiviral particles	Inquiry

Cat.No.	Product Name	Price
SHG040911	shRNA set against Rat Adar(NM_031006.1)	Inquiry
SHH232030	shRNA set against Human ADAR (NM_001111.4)	Inquiry
SHH232034	shRNA set against Mouse ADAR (NM_019655.3)	Inquiry
SHH232038	shRNA set against Rat ADAR (NM_031006.1)	Inquiry
SHW015023	shRNA set against Danio rerio ADAR (NM_131596)	Inquiry

Cat.No.	Product Name	Price
CDCR379504	Rat Adar ORF Clone(NM_031006.1)	Inquiry
CDFR012482	Rat Adar cDNA Clone(NM_031006.1)	Inquiry
MiUTR1R-00127	ADAR miRNA 3'UTR clone	Inquiry
MiUTR3H-01164	ADAR miRNA 3'UTR clone	Inquiry
SKO0285	ADAR Validated sgRNA vector	Inquiry
CDCB176498	Danio rerio ADAR ORF Clone (NM_131596)	Inquiry
CDCB189622	Rabbit ADAR ORF clone (XM_008264373.1)	Inquiry
CDCR024764	Mouse Adar ORF clone (NM_001038587.4)	Inquiry
CDCR024766	Mouse Adar ORF clone (NM_001146296.1)	Inquiry
CDCR254122	Mouse Adar ORF Clone(NM_019655.3)	Inquiry
CDCR299876	Human ADAR ORF Clone(NM_015840.3)	Inquiry

Detailed Information

Adenosineto inosineacting on RNA enzyme (ADAR) is one of the members of the RNA editing enzyme family, which converts the adenosine in the double-stranded RNA into hypoxanthine, recognizes hypoxanthine as a guanine, and paires with cytosine.

The ADAR family consists of three main members: ADAR1, ADAR2 and ADAR3, which are highly maintained in the vertebrate gene sequence. ADAR1 and ADAR2 are widely expressed, while ADAR3 is only found in animal brain tissue. ADAR1 is the most well-defined RNA editing enzyme of biological function. It was first discovered that ADAR1 has two subtypes, namely full-length p150 and shorter p110. Subsequently, Nie et al. found that ADAR1 has the third subtype p80. The existence, structure and function of the three subtypes are different. The p150 gene is induced to be transcribed and translated by interferon, and p110 and p80 can be directly synthesized. P150 mainly exists in the cytoplasm, p110 exists in the nucleus, and p80 exists in the nucleolus.

ADAR1 Biological Function

Research found that ADAR1 editing prevents the recognition of endogenous double-stranded RNA by MDA5 (an intracellular sensor of double-stranded RNA) and is an important new mechanism for the immune system to distinguish between self and non-dsRNA. ADAR1 interacting proteins are mainly divided into two categories: one is the early discovery of interacting proteins that can be edited by ADAR1, such as PKR; the other is a protein independent of editing function that interacts directly with ADAR1, such as nuclear factor, NF45, NF90. Subsequent research found that frameshift mutant protein 1 (Upf1) and Dicer enzyme [one of the RNA-induced gene silencing complex (RISC) members] also can interact with ADAR1 in the body.

In the absence of ADAR1, endogenous dsRNA stimulates the cytosolic RNA receptor to induce an innate immune response. By introducing a mismatched I-U base pair into the RNA transcript, ADAR1 alters the dsRNA structure and perfectly replaces the A-U pair in the dsRNA. If the edit is sufficient to counteract all immunologically active RNA, the corresponding receptor will remain unstimulated. If RNA editing is less efficient, the edited dsRNA will require high capacity to inhibit stimulation from unedited immunologically active RNAs.

ADAR Figure 1. Hypothesis of the mechanism by which cellular endogenous RNA edited by ADAR1 silences cytosolic RNA sensing signaling pathway. (Wang, et al. 2017)

The editing activity of ADAR1 is closely related to the occurrence and development of human diseases. ADAR1-mediated editing dysfunction can cause genetic diseases, autoimmune diseases, neurological diseases, cardiovascular diseases, and cancer. In recent years, more and more studies have found that abnormal editing and expression of ADAR1 have a great influence on the occurrence and development of tumors, such as chronic myeloid leukemia, esophageal cancer, malignant melanoma and liver cancer. It may become a biomarker for certain tumors. Therefore, existing studies attempted to centrally modify ADAR1 activity in vivo and correct RNA editing functions, and found that the ADAR deaminase domain can be used as a potential new tool for correcting genetic diseases of unrelated RNA editing events.

ADAR1 and siRNA

siRNA is a small RNA molecule of approximately 25 nucleotides in length, which is processed by Dicer. Heale et al. found in Drosophila that ADAR1p150 binds to short dsRNA under Dicer-2 excision and competes with Dicer for long dsRNA, inhibiting siRNA synthesis. Studies found that ADAR1p150 binds tightly to siRNA in mouse fibroblast cytoplasm. The effect of siRNA gene silencing on ADAR1 homozygous null mutation is more pronounced than that of wild-type cells, and the results indicate that ADAR1p150 acts as a cytokine that limits siRNA potency (eg, P19) and binds it to RISC by reducing siRNA synthesis in mammalian cells. Another study revealed that A-to-IRNA editing and RNAi complexes can interact with dsRNA through competition and affect siRNA synthesis. In short, ADAR1's full-length subunit p150 can specifically bind to siRNA, limiting siRNA interference efficiency.

ADAM10 and Cancer

Chen et al. found that RNA editing events of antizyme inhibitor 1 (AZIN1) in liver cancer increased and were associated with the development of liver cancer. The RNA editing of AZIN1 catalyzed by ADAR1 replaces the serine encoded by the 376 locus of the gene with glycine, resulting in a change in the conformation of the original encoded protein, thereby increasing the affinity of the anti-enzyme protein; while anti-enzymatic proteins regulate cell growth by binding to growth-promoting proteins (such as ODC1 and CCND1) to induce degradation. The edited AZIN1 promotes hepatoma cell proliferation by blocking the anti-enzyme protein-mediated degradation of oncoproteins ornithine decarboxylase 1 (OCC1) and cyclin D1 (CCND1).

Chan et al. found that patients with liver cancer who had low expression of ADAR1 and low expression of ADAR2 had an increased risk of cirrhosis and postoperative recurrence and had a poor prognosis. Differential expression of ADAR1 and ADAR2 alters gene-specific coding activities, which appears to be associated with high RNA editing of filagin B (FLNB) and coater protein complex subunit α (COPα). RNA editing phenomena are mapped and closely related to the pathogenesis of liver cancer. In addition, functional analysis in vitro and in vivo confirmed that ADAR1 has oncogene function in liver cancer, while ADAR2 has tumor suppressor ability.

References:

Liddicoat, B. J., Piskol, R., Chalk, A. M., Ramaswami, G., Higuchi, M., & Hartner, J. C., et al. (2015). Rna editing by adar1 prevents mda5 sensing of endogenous dsrna as nonself. Science, 349(6252), 1115-20.
Ota, H., Sakurai, M., Gupta, R., Valente, L., Wulff, B. E., & Ariyoshi, K., et al. (2013). Adar1 forms a complex with dicer to promote microrna processing and rna-induced gene silencing. Cell, 153(3), 575-589.
Stellos, K., Gatsiou, A., Stamatelopoulos, K., Perisic, M. L., John, D., & Lunella, F. F., et al. (2016). Adenosine-to-inosine rna editing controls cathepsin s expression in atherosclerosis by enabling hur-mediated post-transcriptional regulation. Nature Medicine, 22(10), 1140.
Tomaselli, S., Bonamassa, B., Alisi, A., Nobili, V., Locatelli, F., & Gallo, A. (2013). Adar enzyme and mirna story: a nucleotide that can make the difference. International Journal of Molecular Sciences, 14(11), 22796-816.
Wang, Q., Li, X., Qi, R., & Billiar, T. (2017). Rna editing, adar1, and the innate immune response: Genes, 8(1), 41.
Liu, W. H., Chen, C. H., Yeh, K. H., Li, C. L., Wu, Y. J., & Chen, D. S., et al. (2013). Adar2-mediated editing of mir-214 and mir-122 precursor and antisense rna transcripts in liver cancers. Plos One, 8(12), e81922.

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