ADAR

Enzyme involved in RNA editing

ADAR

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Crystal structure of ADAR enzyme

Adenosine Deaminase Acting on RNA (ADAR) is an enzyme that catalyzes the conversion of adenosine to inosine in double-stranded RNA (dsRNA). 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) in RNA, ADARs can alter the coding potential of mRNAs, affect RNA splicing, and influence RNA stability and localization. Inosine is interpreted 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: Ubiquitously expressed and involved in editing of both coding and non-coding RNAs. It has two isoforms, p110 and p150, which differ in their cellular localization and function.
• ADAR2: Primarily expressed in the brain and is crucial for editing of specific neurotransmitter receptor mRNAs, such as the glutamate receptor subunit GluR-B.
• ADAR3: Expressed in the brain, but its specific functions are less well understood compared to ADAR1 and ADAR2.

Biological Importance

RNA editing by ADARs is essential for normal development and function of the nervous system. For example, editing of the GluR-B receptor by ADAR2 is critical for proper synaptic transmission and plasticity. Dysregulation of ADAR activity has been implicated in various diseases, including neurological disorders, cancer, and autoimmune diseases.

Mechanism

ADAR enzymes bind to dsRNA regions and deaminate adenosine residues to inosine. The editing sites are often located within specific sequence motifs, and the efficiency of editing can be influenced by the surrounding RNA structure and sequence context.

Clinical Significance

Mutations or altered expression of ADAR genes can lead to disease. For instance, mutations in ADAR1 are associated with Aicardi-Goutières syndrome, a rare genetic disorder that mimics congenital viral infection. Additionally, aberrant RNA editing has been observed in various cancers, suggesting a potential role for ADARs in tumorigenesis.

Research and Therapeutic Potential

Understanding the mechanisms and consequences of RNA editing by ADARs is an active area of research. There is interest in targeting ADARs for therapeutic purposes, such as correcting pathogenic RNA editing events or modulating immune responses.

Also see

• RNA editing
• Inosine
• Glutamate receptor
• Aicardi-Goutières syndrome
• Neurological disorders