The Regulatory Network of METTL3 in the Nervous System: Diagnostic Biomarkers and Therapeutic Targets

Abstract

Methyltransferase-like 3 (METTL3) is a typical component of N6-methyladenosine writers that exhibits methyltransferase activity and deposits methyl groups on RNA. Currently, accumulating studies have demonstrated the involvement of METTL3 in the regulation of neuro-physiological and pathological events. However, no reviews have comprehensively summarized and analyzed the roles and mechanisms of METTL3 in these events. Herein, we are focused on reviewing the roles of METTL3 in regulating normal neurophysiological (Neurogenesis, Synaptic Plasticity and Glial Plasticity, Neurodevelopment, Learning and Memory,) and neuropathological (Autism Spectrum Disorder, Major Depressive Disorder, Neurodegenerative disorders, Brain Tumors, Brain Injuries, and Other Brain Disorders) events. Our review found that although the down-regulated levels of METTL3 function through different roles and mechanisms in the nervous system, it primarily inactivates neuro-physiological events and triggers or worsens neuropathological events. In addition, our review suggests that METTL3 could be used as a diagnostic biomarker and therapeutic target in the nervous system. Collectively, our review has provided an up-to-date research outline of METTL3 in the nervous system. In addition, the regulatory network for METTL3 in the nervous system has been mapped, which could provide directions for future research, biomarkers for clinical diagnosis, and targets for disease treatment. Furthermore, this review has provided a comprehensive view, which could improve our understanding of METTL3 functions in the nervous system.

Methyltransferase‐like 3 mediated RNA m6A modifications in the reproductive system: Potentials for diagnosis and therapy

“…The m 6 A modification of RNAs primarily relies on the function of METTL3, which affects various biological processes, including its widespread involvement in the reproductive system 5 . In this review, studies exploring the roles and mechanisms of METTL3 in the reproductive system are comprehensively summarized and interpreted with the aim of elucidating the intricate relationships and potential applications of METTL3 in the reproductive system.…”

“…Differences in gene expression or phenotype occurrence may be attributed to epigenetic modifications, such as the prevalent N 6 methyladenosine (m 6 A) modification of RNA molecules, which has received increasing attention in the investigation of the mechanism of biological processes. 4,5 RNA m 6 A is one of the most prominent epigenetic modification, and is associated with three regulatory factors: writers, erasers and readers. 4,5 Writers are commonly known for the activity of methyltransferases to add methyl groups (-CH 3 ), whereas erasers are primarily demethylases with the opposite ability, to remove -CH 3 , and readers primarily recognize m 6 A RNA and decide the fate of RNA.…”

“…4,5 RNA m 6 A is one of the most prominent epigenetic modification, and is associated with three regulatory factors: writers, erasers and readers. 4,5 Writers are commonly known for the activity of methyltransferases to add methyl groups (-CH 3 ), whereas erasers are primarily demethylases with the opposite ability, to remove -CH 3 , and readers primarily recognize m 6 A RNA and decide the fate of RNA. 4,5 Writers, also called m 6 A methyltransferase complex, consists of a multicomponent that is primarily installed by methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14), as well as some other regulatory subunits such as the Wilms' tumour 1 (WT1) associated protein (WTAP).…”

“…Differences in gene expression or phenotype occurrence may be attributed to epigenetic modifications, such as the prevalent N 6 ‐methyladenosine (m 6 A) modification of RNA molecules, which has received increasing attention in the investigation of the mechanism of biological processes 4,5 . RNA m 6 A is one of the most prominent epigenetic modification, and is associated with three regulatory factors: writers, erasers and readers 4,5 .…”

Effect of RNA m6A methyltransferase activation by a low molecular weight compound on anxiety- and depression-related behaviours, monoamine neurochemistry and striatal gene expression in the rat

“…m 6 A modification occurs in all organs but is particularly abundant in mammalian brain. There is increasing evidence on how mRNA m 6 A methylation is involved in regulation of behaviour, suggestive that its dysregulation may contribute to the development of and pathogenesis of neuropsychiatric disorders (Zaccara et al 2019; Livneh et al, 2020; Selberg et al, 2021; Shafik et al, 2022; Su et al, 2023).…”