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.'
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Proteins (1)

Compounds (15)