Recombinant Mouse Double-stranded RNA-specific adenosine deaminase (Adar), partial

Function

Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins since the translational machinery read the inosine as a guanosine; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2) and serotonin (HTR2C) and GABA receptor (GABRA3). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alters their functional activities. Exhibits low-level editing at the GRIA2 Q/R site, but edits efficiently at the R/G site and HOTSPOT1. Does not affect polyomavirus replication but provides protection against virus-induced cytopathic effects. Essential for embryonic development and cell survival and plays a critical role in the maintenance of hematopoietic stem cells

Subcellular Location

Nucleus, nucleolus

Tissue Specificity

Highest levels in brain and spleen. Lowest levels in liver

Subunit

Homodimer. Homodimerization is essential for its catalytic activity (PubMed:12618436). Isoform 5 can form heterodimers with ADARB1/ADAR2. Isoform 1 and isoform 5 (via DRBM 3 domain) interact with TNPO1. Isoform 5 (via DRBM domains) interacts with XPO5. Isoform 1 and isoform 5 can interact with UPF1 (By similarity). Isoform 1 interacts with ILF2/NF45 and ILF3/NF90 (PubMed:16055709). Binding to ILF3/NF90 up-regulates ILF3-mediated gene expression. Isoform 1 and isoform 5 interact with EIF2AK2/PKR (PubMed:17079286)

• Yang J.-H. et al. Intracellular localization of differentially regulated RNA-specific adenosine deaminase isoforms in inflammation. — J. Biol. Chem. (2003)
• Yang J.-H. et al. Widespread inosine-containing mRNA in lymphocytes regulated by ADAR1 in response to inflammation. — Immunology (2003)
• Young S.B. et al. cDNA for mouse double-stranded RNA-specific adenosine deaminase (ADAR1). (MAR-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Carninci P. et al. The transcriptional landscape of the mammalian genome. — Science (2005)
• Cho D.-S.C. et al. Requirement of dimerization for RNA editing activity of adenosine deaminases acting on RNA. — J. Biol. Chem. (2003)
• Hartner J.C. et al. Liver disintegration in the mouse embryo caused by deficiency in the RNA-editing enzyme ADAR1. — J. Biol. Chem. (2004)
• Wang Q. et al. Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene. — J. Biol. Chem. (2004)