Adar Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Property | Value |
|----------|-------|
| **Protein Name** | ADAR (RNA-specific adenosine deaminase) |
| **Gene** | ADAR |
| **UniProt ID** | P55265 |
| **PDB ID** | 5HPJ, 6AKM |
| **Molecular Weight** | ~122 kDa |
| **Subcellular Localization** | Nucleus, Cytoplasm |
| **Protein Family** | Adenosine deaminase family |
| **Aliases** | ADAR1, A-to-I editing enzyme, dsRNA-specific adenosine deaminase |
The ADAR protein contains multiple functional domains:
- N-terminal dsRNA binding domains (dsRBDs): Three dsRBDs (dsRBD1, dsRBD2, dsRBD3) that recognize and bind to double-stranded RNA
- Z-DNA binding domain (Zα): Binds to left-handed Z-DNA structures
- Deaminase domain: The catalytic domain that performs adenosine deamination
The catalytic deaminase domain belongs to the metalloenzyme superfamily and requires zinc ions for catalytic activity. The protein can form homodimers, which is important for its enzymatic function.
ADAR (adenosine deaminase acting on RNA) is a dsRNA-specific adenosine deaminase that catalyzes the hydrolytic deamination of adenosine to inosine (A-to-I editing) in RNA molecules. This is the most prevalent form of RNA editing in mammals.
- A-to-I editing: Catalyzes the conversion of adenosine to inosine in double-stranded RNA regions
- RNA splicing regulation: Editing within intronic regions can alter splice site selection
- MiRNA biogenesis: Editing of pri-miRNA and pre-miRNA affects processing by Dicer
- Innate immunity: Editing of self-RNA prevents inappropriate activation of MDA5-mediated interferon responses
- Epigenetic regulation: Inosine-containing RNAs can influence chromatin remodeling
ADAR preferentially edits:
- Long dsRNA regions (>40 bp)
- Stem-loop structures in pre-mRNAs and miRNA precursors
- Non-coding RNAs including Alu repeats in human transcripts
- GRIA2 editing: ADAR-mediated editing of the GRIA2 (GluA2) AMPA receptor subunit is reduced in AD brain, leading to increased Ca²⁺ influx through unedited channels
- RNA metabolism: Global reduction in A-to-I editing in AD temporal cortex
- Tau pathology: Tau accumulation may affect ADAR localization and activity
- Excitotoxicity: Reduced GRIA2 editing in ALS motor neurons contributes to excitotoxic cell death
- RNA granules: ADAR activity is affected by stress granule dynamics in ALS
- SOD1 editing: Potential editing of SOD1 transcripts may influence aggregation
- Huntington's disease: Altered editing patterns in HD striatum
- Epilepsy: ADAR2 activity is dysregulated in epileptic tissue
- Aicardi-Goutières syndrome: Loss-of-function mutations cause autoimmune encephalopathy
| Approach |
Status |
Description |
| Small molecule activators |
Preclinical |
Compounds that enhance ADAR activity |
| RNA-based therapies |
Research |
siRNA to modulate ADAR expression |
| Gene therapy |
Research |
AAV-mediated delivery of ADAR |
| Editing reporters |
Diagnostic |
Measuring ADAR activity as biomarker |
[1] Slot, L.M. et al. (2020). Altered A-to-I RNA editing in Alzheimer's disease. Nat Neurosci 23, 1287-1293.
[2] Hideyama, T. et al. (2010). Profound loss of GRIA2 editing in amyotrophic lateral sclerosis. J Neurosci 30, 16042-16051.
[3] Orlandi, C. et al. (2021). ADAR-mediated RNA editing in neurodegenerative diseases. Prog Neurobiol 205, 101984.
[4] Goodman, R.H. & Im, H. (2019). ADAR-mediated RNA editing in brain. Neuron 101, 10-14.
The study of Adar Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Bass, B.L. (2002). The role of ADAR in RNA editing. Annu Rev Biochem 71, 817-846. PMID:12045112.
- Nishikura, K. (2016). A-to-I editing of coding and non-coding RNAs by ADARs. Nat Rev Mol Cell Biol 17, 83-96. PMID:26648264.
- George, C.F. (2021). ADAR mediated RNA editing in the nervous system. Mol Cell Neurosci 113, 103591. PMID:33745876.
- Hogg, M. et al. (2011). ADAR proteins: structure and function in RNA editing. Cold Spring Harb Perspect Biol 3, a002477. PMID:20943777.
- Samuel, C.E. (2019). ADARs: viruses and interferon. Curr Opin Immunol 56, 30-35. PMID:30412856.