Adarb1-KO Mouse

Adarb1, also named ADAR2, is an adenosine-to-inosine (A-to-I) RNA-editing enzyme. A-to-I RNA editing is a crucial post-transcriptional modification, which can affect RNA stability, translation, and protein-coding potential, thus participating in various biological processes. ADARB1 has been shown to be involved in regulating neurotransmitter receptors and may be associated with the mitochondrial respiratory chain complex [2].

In cancer research, downregulated ADARB1 expression was found in lung adenocarcinoma, lung squamous cell carcinoma, and ovarian cancer, and it was related to tumor cell metastasis, shorter survival times, and cell proliferation [1,3,6]. In glioblastoma, ADARB1 was upregulated and involved in AKT-mediated temozolomide resistance [2]. In hepatocellular carcinoma treated with transarterial chemoembolization, ADARB1 polymorphisms were associated with prognosis [7].

In neurological research, bi-allelic variants in ADARB1 were associated with microcephaly, intellectual disability, and epilepsy, as these variants led to reduced ADAR2 editing activity [4,8].

In circadian rhythm research, Adarb1-knockout mice exhibited attenuated mRNA rhythms, short-period rhythms in locomotor activity, and abnormal accumulation of CRY2, indicating ADARB1's role in post-transcriptional regulation of the circadian clock [5].

In conclusion, ADARB1 is an essential RNA-editing enzyme with a wide-reaching impact on biological processes. Its role in various diseases, especially cancer and neurological disorders, has been revealed through studies including gene-knockout models. Understanding ADARB1's function helps to better understand disease mechanisms and may provide potential therapeutic targets.

References:

1. Wang, Xiang, Xu, Zhijie, Ren, Xinxin, Gong, Zhicheng, Yan, Yuanliang. 2019. Function of low ADARB1 expression in lung adenocarcinoma. In PloS one, 14, e0222298. doi:10.1371/journal.pone.0222298. https://pubmed.ncbi.nlm.nih.gov/31491024/

2. Lu, Can, Chen, Xi, Yan, Yuanliang, Xu, Zhijie, Peng, Jinwu. 2022. Aberrant Expression of ADARB1 Facilitates Temozolomide Chemoresistance and Immune Infiltration in Glioblastoma. In Frontiers in pharmacology, 13, 768743. doi:10.3389/fphar.2022.768743. https://pubmed.ncbi.nlm.nih.gov/35177985/

3. Wang, Xiang, Ren, Xinxin, Liu, Wanli, Yan, Yuanliang, Xu, Zhijie. 2020. Role of downregulated ADARB1 in lung squamous cell carcinoma. In Molecular medicine reports, 21, 1517-1526. doi:10.3892/mmr.2020.10958. https://pubmed.ncbi.nlm.nih.gov/32016472/

4. Tan, Tiong Yang, Sedmík, Jiří, Fitzgerald, Mark P, Christodoulou, John, O'Connell, Mary A. 2020. Bi-allelic ADARB1 Variants Associated with Microcephaly, Intellectual Disability, and Seizures. In American journal of human genetics, 106, 467-483. doi:10.1016/j.ajhg.2020.02.015. https://pubmed.ncbi.nlm.nih.gov/32220291/

5. Terajima, Hideki, Yoshitane, Hikari, Ozaki, Haruka, Iwasaki, Wataru, Fukada, Yoshitaka. 2016. ADARB1 catalyzes circadian A-to-I editing and regulates RNA rhythm. In Nature genetics, 49, 146-151. doi:10.1038/ng.3731. https://pubmed.ncbi.nlm.nih.gov/27893733/

6. Zhu, Wei, Xu, Zhijie, Huang, Meiyuan, Chen, Xi, Yan, Yuanliang. 2021. Downregulated ADARB1 Facilitates Cell Proliferation, Invasion and has Effect on the Immune Regulation in Ovarian Cancer. In Frontiers in bioengineering and biotechnology, 9, 792911. doi:10.3389/fbioe.2021.792911. https://pubmed.ncbi.nlm.nih.gov/35004651/

7. Zeng, Jiajia, Han, Linyu, Wang, Teng, Li, Ziqiang, Yang, Ming. 2023. The Allelic Expression of RNA Editing Gene ADARB1 in Hepatocellular Carcinoma Treated with Transarterial Chemoembolization. In Pharmacogenomics and personalized medicine, 16, 229-238. doi:10.2147/PGPM.S402115. https://pubmed.ncbi.nlm.nih.gov/36970122/

8. Maroofian, Reza, Sedmík, Jiří, Mazaheri, Neda, O'Connell, Mary A, Houlden, Henry. 2020. Biallelic variants in ADARB1, encoding a dsRNA-specific adenosine deaminase, cause a severe developmental and epileptic encephalopathy. In Journal of medical genetics, 58, 495-504. doi:10.1136/jmedgenet-2020-107048. https://pubmed.ncbi.nlm.nih.gov/32719099/