Anti-ADAR1: Rabbit ADAR1 Antibody

BACKGROUND The host cell restricts viral replication by a myriad of mechanisms, those induced by type I interferons (IFNs) being among the best known. Both cytidine and adenosine polynucleotide deaminases are induced and can restrict viral replication. For humans, there are 11 genes encoding cytidine deaminases (APOBEC1, APOBEC2, APOBEC3A to -C, -3DE, -3F to -H, APOBEC4, and AID), of which 8 are functional on single-stranded DNA (ssDNA) and only 1 of which is functional on RNA. In contrast, three adenosine deaminases acting on RNA (ADAR-1, -2, and -3) are known, their substrate specificity being double-stranded RNA (dsRNA). Although ADAR-1, -2, and -3 are conserved in their C-terminal catalytic domain as well as in their double-stranded RNA-binding domains, only ADAR-1 and -2 have demonstrable enzymatic activity. They probably evolved from adenosine deaminases acting on tRNAs after the split between protozoa and metazoa. While mammalian ADAR-1 and ADAR-2 are ubiquitously expressed in many tissues, ADAR-3 was limited to the nervous system.¹

ADAR1 (adenosine deaminase acting on RNA) is an RNA-specific C-6 adenosine deaminase that catalyzes the conversion of adenosine (A) to inosine (I) on RNAs with double-stranded character. Such “A-to-I editing” by ADAR1 is of broad biologic importance, because I is recognized as G instead of A by ribosomes and polymerases. This editing event can change both the sequence and the secondary structure of RNA molecules, with important consequences on both the final proteins and regulatory RNAs. Alteration in RNA editing has been connected to numerous human pathologies and recent studies have demonstrated its importance in tumor progression. At the same time, ADAR1 plays an important role in the nervous system, where site-specific editing of glutamate receptor and serotonin-2C receptor pre-mRNAs changes their coding capacity, thereby leading to neurotransmitter receptor protein products with altered physiological properties. In addition, ADAR1 is involved in the RNA interference pathway and is known to alter both the targeting and the processing of microRNAs. Furthermore, RNA editing patterns characteristic of ADAR enzymes have been detected in several viral RNAs, including those of measles virus, influenza virus, lymphocytic choriomeningitis virus, polyomavirus, hepatitis delta virus, and hepatitis C virus.² ADAR1 is encoded by a single-copy gene that maps to human chromosome 1q21. The domain structure of the ADAR1 protein product includes the C-terminal deaminase catalytic domain, three centrally located dsRNA binding domains, and one or two N-terminal Z-DNA binding domains. Two size forms of the ADAR1 protein are known. One, p110, is constitutively expressed and found predominantly in the nucleus of cells; the other, p150, is interferon (IFN)-inducible and is found in both the nucleus and the cytoplasm. Compared with p110, the p150 form of human ADAR1 possesses an additional 295 N-terminal amino acids. The function of the N-terminal extension of p150 is not entirely understood, but the region contains a nuclear export signal and an additional Z-DNA binding domain. Because of its regulation by IFN and cytoplasmic localization, the p150 version of ADAR1 is thought to be the form responsible for the A-to-I editing of viral RNAs produced by viruses that replicate in the cytoplasm of infected cells.³
 

REFERENCES  

1. Nishikura, K.: Annu. Rev. Biochem. 79:321-49, 2010
2. Hundley, H.A. & Bass, B.L.: Trends Biochem. Sci. 35:377-83, 2010
3. Jin, Y. et al: IUBMB Life. 61:572-8, 2009