ADAR

Enzyme involved in RNA editing

Identifiers
EC number	3.5.4.37
CAS number	9026-93-1
Alt. names
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway

Adenosine Deaminase Acting on RNA (ADAR) is an enzyme that catalyzes the conversion of adenosine to inosine in double-stranded RNA (dsRNA) molecules. This process is known as RNA editing, and it plays a crucial role in the regulation of gene expression and the diversification of the transcriptome.

Function

ADAR enzymes are responsible for the post-transcriptional modification of RNA molecules. By converting adenosine (A) to inosine (I), ADARs can alter the coding potential of mRNA, affect RNA splicing, and influence RNA stability and localization. Inosine is recognized as guanosine (G) by the cellular machinery, which can lead to changes in the amino acid sequence of proteins, potentially altering their function.

Types of ADAR

There are three main types of ADAR enzymes in humans:

• ADAR1: This enzyme is ubiquitously expressed and has two isoforms, p110 and p150, which are produced by alternative splicing. ADAR1 is involved in editing of both coding and non-coding RNAs and plays a role in the innate immune response.

• ADAR2: Primarily expressed in the brain, ADAR2 is essential for the editing of specific neurotransmitter receptor subunits, such as the glutamate receptor subunit GluR-B. This editing is crucial for normal brain function and development.

• ADAR3: The function of ADAR3 is less well understood, but it is predominantly expressed in the brain and is thought to have a regulatory role in RNA editing.

Biological Significance

RNA editing by ADARs is important for several biological processes:

• Neurotransmission: Editing of neurotransmitter receptor mRNAs by ADARs can affect synaptic transmission and plasticity, influencing learning and memory.

• Immune Response: ADAR1 is involved in the regulation of the innate immune response by editing viral RNAs and endogenous dsRNAs, preventing inappropriate activation of immune pathways.

• Development: Proper RNA editing is essential for normal development, particularly in the nervous system.

Clinical Implications

Dysregulation of ADAR activity has been implicated in various diseases:

• Neurological Disorders: Aberrant RNA editing is associated with neurological conditions such as epilepsy, amyotrophic lateral sclerosis (ALS), and schizophrenia.

• Cancer: Altered ADAR expression and RNA editing patterns have been observed in several cancers, suggesting a role in tumorigenesis.

• Autoimmune Diseases: Defects in ADAR1 can lead to autoimmune disorders due to improper regulation of the immune response.

Research and Future Directions

Ongoing research aims to further elucidate the mechanisms of ADAR-mediated RNA editing and its implications in health and disease. Potential therapeutic strategies include targeting ADARs to modulate RNA editing in specific diseases.

Also see

• RNA editing
• Inosine
• Gene expression
• Neurotransmitter receptor
• Innate immune system