|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|
|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|
|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|
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.
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.
Our promise to you:
Guaranteed product quality, expert customer support.
Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.