mRNA N6-methyladenosine dioxygenase activity
Definition
Target type: molecularfunction
Catalysis of the oxidative demethylation of N6-methyladenosine RNA, with concomitant decarboxylation of 2-oxoglutarate and releases oxidized methyl group on N6-methyladenosine as formaldehyde. [PMID:22002720, PMID:26458103]
mRNA N6-methyladenosine dioxygenase activity refers to the enzymatic process that removes the N6-methyl group from adenosine residues within mRNA molecules. This modification, known as N6-methyladenosine (m6A), is a widespread and critical epigenetic mark found in eukaryotic mRNA, influencing various aspects of RNA metabolism, including translation, stability, and splicing.
m6A dioxygenases, also called FTO and ALKBH5, catalyze the oxidative demethylation of m6A, converting it back to adenosine (A). This process is crucial for regulating the dynamic and reversible nature of m6A modifications, allowing for fine-tuning of mRNA function in response to cellular cues.
The catalytic mechanism involves the binding of an m6A-containing RNA substrate to the enzyme's active site. The enzyme then utilizes a ferrous iron cofactor and molecular oxygen to initiate a series of reactions, resulting in the removal of the methyl group and the formation of formaldehyde as a byproduct.
The precise molecular function of m6A dioxygenases varies depending on the specific RNA target and cellular context. However, several key roles have been identified:
* **Regulation of mRNA Translation:** m6A dioxygenases can influence the translation efficiency of target mRNAs by modulating their association with ribosomes. Removal of m6A can promote translation, whereas its presence can inhibit it.
* **Control of mRNA Stability:** m6A demethylation can impact the stability of mRNA molecules. Demethylation can promote mRNA decay, while the presence of m6A can stabilize the molecule, extending its lifetime.
* **Modulation of mRNA Splicing:** m6A dioxygenases can influence alternative splicing events, affecting the production of different protein isoforms from a single gene. Demethylation can alter splicing patterns, leading to the expression of distinct protein variants.
In summary, mRNA N6-methyladenosine dioxygenase activity plays a critical role in controlling the dynamic landscape of m6A modifications within mRNA molecules, ultimately influencing various aspects of RNA metabolism and gene expression. This enzymatic process is essential for maintaining cellular homeostasis and responding to diverse physiological stimuli.'
"
Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Alpha-ketoglutarate-dependent dioxygenase FTO | An alpha-ketoglutarate-dependent dioxygenase FTO that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9C0B1] | Homo sapiens (human) |
Compounds (15)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| citric acid, anhydrous | citric acid : A tricarboxylic acid that is propane-1,2,3-tricarboxylic acid bearing a hydroxy substituent at position 2. It is an important metabolite in the pathway of all aerobic organisms. Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. | tricarboxylic acid | antimicrobial agent; chelator; food acidity regulator; fundamental metabolite |
| malic acid | 2-hydroxydicarboxylic acid : Any dicarboxylic acid carrying a hydroxy group on the carbon atom at position alpha to the carboxy group. malic acid : A 2-hydroxydicarboxylic acid that is succinic acid in which one of the hydrogens attached to a carbon is replaced by a hydroxy group. | 2-hydroxydicarboxylic acid; C4-dicarboxylic acid | food acidity regulator; fundamental metabolite |
| pyruvic acid | pyruvic acid : A 2-oxo monocarboxylic acid that is the 2-keto derivative of propionic acid. It is a metabolite obtained during glycolysis. Pyruvic Acid: An intermediate compound in the metabolism of carbohydrates, proteins, and fats. In thiamine deficiency, its oxidation is retarded and it accumulates in the tissues, especially in nervous structures. (From Stedman, 26th ed) | 2-oxo monocarboxylic acid | cofactor; fundamental metabolite |
| 2,4-pyridinedicarboxylic acid | lutidinic acid : A pyridinedicarboxylic acid carrying carboxy groups at positions 2 and 4. | pyridinedicarboxylic acid | |
| d-glutamate | D-alpha-amino acid; glutamic acid | Escherichia coli metabolite; mouse metabolite | |
| glutamic acid | glutamic acid : An alpha-amino acid that is glutaric acid bearing a single amino substituent at position 2. Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM. | glutamic acid; glutamine family amino acid; L-alpha-amino acid; proteinogenic amino acid | Escherichia coli metabolite; ferroptosis inducer; micronutrient; mouse metabolite; neurotransmitter; nutraceutical |
| d-lactic acid | (R)-lactic acid : An optically active form of lactic acid having (R)-configuration. | 2-hydroxypropanoic acid | Escherichia coli metabolite; human metabolite |
| d-2-hydroxyglutarate | (R)-2-hydroxyglutaric acid : The (R)-enantiomer of 2-hydroxyglutaric acid. | 2-hydroxyglutaric acid | algal metabolite |
| alpha-hydroxyglutarate, (l)-isomer | 2-hydroxyglutaric acid | ||
| fumaric acid | fumaric acid : A butenedioic acid in which the C=C double bond has E geometry. It is an intermediate metabolite in the citric acid cycle. fumaric acid: see also record for ferrous fumarate; use FUMARATES for general fumaric acid esters | butenedioic acid | food acidity regulator; fundamental metabolite; geroprotector |
| 5-carboxy-8-hydroxyquinoline | 5-carboxy-8-hydroxyquinoline: a JmjC histone demethylase inhibitor; structure in first source | quinolines | |
| aconitic acid | cis-aconitic acid : The cis-isomer of aconitic acid. | aconitic acid | fundamental metabolite |
| oxalylglycine | N-oxalylglycine : An amino dicarboxylic acid that is iminodiacetic acid with an oxo substituent. It is used as an inhibitor of alpha-ketoglutarate dependent (EC 1.14.11.*) enzymes. oxalylglycine: structure given in first source | amino dicarboxylic acid; N-acylglycine | EC 1.14.11.* (oxidoreductase acting on paired donors, 2-oxoglutarate as one donor, incorporating 1 atom each of oxygen into both donors) inhibitor |
| entacapone | entacapone : A monocarboxylic acid amide that is N,N-diethylprop-2-enamide in which the hydrogen at position 2 is substituted by a cyano group and the hydrogen at the 3E position is substituted by a 3,4-dihydroxy-5-nitrophenyl group. entacapone: structure given in first source | 2-nitrophenols; catechols; monocarboxylic acid amide; nitrile | antidyskinesia agent; antiparkinson drug; central nervous system drug; EC 2.1.1.6 (catechol O-methyltransferase) inhibitor |
| fg-4592 | roxadustat : An N-acylglycine resulting from the formal condensation of the amino group of glycine with the carboxy group of 4-hydroxy-1-methyl-7-phenoxyisoquinoline-3-carboxylic acid. It is an inhibitor of hypoxia inducible factor prolyl hydroxylase (HIF-PH). roxadustat: structure in first source | aromatic ether; isoquinolines; N-acylglycine | EC 1.14.11.2 (procollagen-proline dioxygenase) inhibitor; EC 1.14.11.29 (hypoxia-inducible factor-proline dioxygenase) inhibitor |