The Progression of N6-methyladenosine Study and Its Role in Neuropsychiatric Disorders

Abstract

Epitranscriptomic modifications can affect every aspect of RNA biology, including stability, transport, splicing, and translation, participate in global intracellular mRNA metabolism, and regulate gene expression and a variety of biological processes. N6-methyladenosine (m6A) as the most prevalent modification contributes to normal embryonic brain development and memory formation. However, changes in the level of m6A modification and the expression of its related proteins cause abnormal nervous system functions, including brain tissue development retardation, axon regeneration disorders, memory changes, and neural stem cell renewal and differentiation disorders. Recent studies have revealed that m6A modification and its related proteins play key roles in the development of various neuropsychiatric disorders, such as depression, Alzheimer’s disease, and Parkinson’s disease. In this review, we summarize the research progresses of the m6A modification regulation mechanism in the central nervous system and discuss the effects of gene expression regulation mediated by m6A modification on the biological functions of the neuropsychiatric disorders, thereby providing some insight into new research targets and treatment directions for human diseases.

M6A modification promotes blood-brain barrier breakdown during cerebral ischemia/reperfusion injury through increasing matrix metalloproteinase 3 expression

“…M6A modification on mRNA is dynamically regulated by the methyltransferases (Writers) and demethylases (Erasers) [ 15 , 16 ]. Recent study reports the m6A levels in the brain cortex are significantly increased after MCAO/R injury, which is mediated by reduction of the m6A demethylase FTO [ 36 ].…”

“…N 6-methyladenosine (m6A), the most common modification in eukaryotic mRNA, participates in various cellular processes, such as mRNA metabolism, RNA splicing, and protein translation [ 14 ]. M6A modification is catalyzed by the methyltransferases (Writer), and could be removed by the demethylases (Eraser) [ 15 , 16 ]. In addition, m6A is recognized by “reader” proteins to regulate mRNA transcription, decoy, or translation [ 17 ].…”

The Potential Role of m6A in the Regulation of TBI-Induced BGA Dysfunction

“…M 6 A modification is abundant in the brain, normalising the nervous system function by regulating mRNA metabolism. When the expression of key enzymes and/or binding proteins involved in m 6 A modification is abnormal, the level of m 6 A modification may fluctuate, leading to molecular dysfunctions such as mRNA metabolism disorder and transcription and translation disorders that cause physiological dysfunction of the nervous system [ 136 , 137 , 138 ]. Given its diversity and reversibility, m 6 A modification harbours more complicated physiological mechanisms in regulating CNS functions.…”

Hypericin Ameliorates Depression-like Behaviors via Neurotrophin Signaling Pathway Mediating m6A Epitranscriptome Modification

“…Therefore, it is necessary to explore new molecular 2 of 18 mechanisms in the pathogenesis of depression and to develop new antidepressants. Epigenetic modifications of genes play an important role in the development of depression [7][8][9] and, similar to DNA methylation modifications and histone modifications, changes in the homeostasis of m6A modifications may also contribute to depression [10,11]. m6A modifications are among the most common modifications of RNA [12], and this dynamic and reversible modification primarily depends on regulation by methyltransferases and demethylases, including Methyltransferase-like protein 3 (METTL3), Methyltransferase-like protein 14 (METTL14) Wt1 Associated Protein (WTAP) Fat Mass and Obesity-Associated Protein (FTO) and Alkb Homolog 5 (ALKBH5) [11,13].…”

“…The occurrence of depression is closely related to the disruption of m6A modification of RNA caused by changes in the activity or expression of m6A-modifying enzymes [10,11,15,16]. Demethylase FTO expression was found to be markedly downregulated in the blood of depressed patients and in the hippocampus of mice with depressivelike behavior [15].…”