ADAR: Difference between revisions

Latest revision as of 15:30, 9 December 2024

Enzyme involved in RNA editing

ADAR

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[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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-{{Short description|Enzyme involved in RNA editing}}
+[[File:ADAR1 mechanism.png|thumb]] [[File:ADAR reaction.jpg|thumb]] [[File:ADAR1 active site.png|thumb]] {{Short description|Enzyme involved in RNA editing}}
 {{Infobox enzyme
-| name = Adenosine Deaminase Acting on RNA (ADAR)
+| name = Adenosine Deaminase Acting on RNA
-| image = ADAR_structure.png
+| image = <!-- Image of the enzyme, if available -->
-| width = 250
+| width =
-| caption = Crystal structure of ADAR enzyme
+| caption =
 | EC_number = 3.5.4.37
-| CAS_number = 9026-93-5
+| CAS_number = 9026-93-1
 | IUBMB_EC_number = 3/5/4/37
+| GO_code = 0004000
 }}
-'''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.
+'''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) 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.
+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''': 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.
+* '''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 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==
+* '''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.
-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==
+* '''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.
-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==
+==Biological 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.
+RNA editing by ADARs is important for several biological processes:
-==Research and Therapeutic Potential==
+* '''Neurotransmission''': Editing of neurotransmitter receptor mRNAs by ADARs can affect synaptic transmission and plasticity, influencing learning and memory.
-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.
+* '''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]]
-* [[Glutamate receptor]]
+* [[Gene expression]]
-* [[Aicardi-Goutières syndrome]]
+* [[Neurotransmitter receptor]]
-* [[Neurological disorders]]
+* [[Innate immune system]]
 {{Enzymes}}