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Emerging Role of m(6) A Methylome in Brain Development: Implications for Neurological Disorders and Potential Treatment

Dynamic modification of RNA affords proximal regulation of gene expression triggered by non-genomic or environmental changes. One such epitranscriptomic alteration in RNA metabolism is the installation of a methyl group on adenosine [N(6)-methyladenosine (m(6)A)] known to be the most prevalent modif...

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Autores principales: Sokpor, Godwin, Xie, Yuanbin, Nguyen, Huu P., Tuoc, Tran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170044/
https://www.ncbi.nlm.nih.gov/pubmed/34095121
http://dx.doi.org/10.3389/fcell.2021.656849
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author Sokpor, Godwin
Xie, Yuanbin
Nguyen, Huu P.
Tuoc, Tran
author_facet Sokpor, Godwin
Xie, Yuanbin
Nguyen, Huu P.
Tuoc, Tran
author_sort Sokpor, Godwin
collection PubMed
description Dynamic modification of RNA affords proximal regulation of gene expression triggered by non-genomic or environmental changes. One such epitranscriptomic alteration in RNA metabolism is the installation of a methyl group on adenosine [N(6)-methyladenosine (m(6)A)] known to be the most prevalent modified state of messenger RNA (mRNA) in the mammalian cell. The methylation machinery responsible for the dynamic deposition and recognition of m(6)A on mRNA is composed of subunits that play specific roles, including reading, writing, and erasing of m(6)A marks on mRNA to influence gene expression. As a result, peculiar cellular perturbations have been linked to dysregulation of components of the mRNA methylation machinery or its cofactors. It is increasingly clear that neural tissues/cells, especially in the brain, make the most of m(6)A modification in maintaining normal morphology and function. Neurons in particular display dynamic distribution of m(6)A marks during development and in adulthood. Interestingly, such dynamic m(6)A patterns are responsive to external cues and experience. Specific disturbances in the neural m(6)A landscape lead to anomalous phenotypes, including aberrant stem/progenitor cell proliferation and differentiation, defective cell fate choices, and abnormal synaptogenesis. Such m(6)A-linked neural perturbations may singularly or together have implications for syndromic or non-syndromic neurological diseases, given that most RNAs in the brain are enriched with m(6)A tags. Here, we review the current perspectives on the m(6)A machinery and function, its role in brain development and possible association with brain disorders, and the prospects of applying the clustered regularly interspaced short palindromic repeats (CRISPR)–dCas13b system to obviate m(6)A-related neurological anomalies.
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spelling pubmed-81700442021-06-03 Emerging Role of m(6) A Methylome in Brain Development: Implications for Neurological Disorders and Potential Treatment Sokpor, Godwin Xie, Yuanbin Nguyen, Huu P. Tuoc, Tran Front Cell Dev Biol Cell and Developmental Biology Dynamic modification of RNA affords proximal regulation of gene expression triggered by non-genomic or environmental changes. One such epitranscriptomic alteration in RNA metabolism is the installation of a methyl group on adenosine [N(6)-methyladenosine (m(6)A)] known to be the most prevalent modified state of messenger RNA (mRNA) in the mammalian cell. The methylation machinery responsible for the dynamic deposition and recognition of m(6)A on mRNA is composed of subunits that play specific roles, including reading, writing, and erasing of m(6)A marks on mRNA to influence gene expression. As a result, peculiar cellular perturbations have been linked to dysregulation of components of the mRNA methylation machinery or its cofactors. It is increasingly clear that neural tissues/cells, especially in the brain, make the most of m(6)A modification in maintaining normal morphology and function. Neurons in particular display dynamic distribution of m(6)A marks during development and in adulthood. Interestingly, such dynamic m(6)A patterns are responsive to external cues and experience. Specific disturbances in the neural m(6)A landscape lead to anomalous phenotypes, including aberrant stem/progenitor cell proliferation and differentiation, defective cell fate choices, and abnormal synaptogenesis. Such m(6)A-linked neural perturbations may singularly or together have implications for syndromic or non-syndromic neurological diseases, given that most RNAs in the brain are enriched with m(6)A tags. Here, we review the current perspectives on the m(6)A machinery and function, its role in brain development and possible association with brain disorders, and the prospects of applying the clustered regularly interspaced short palindromic repeats (CRISPR)–dCas13b system to obviate m(6)A-related neurological anomalies. Frontiers Media S.A. 2021-05-19 /pmc/articles/PMC8170044/ /pubmed/34095121 http://dx.doi.org/10.3389/fcell.2021.656849 Text en Copyright © 2021 Sokpor, Xie, Nguyen and Tuoc. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Sokpor, Godwin
Xie, Yuanbin
Nguyen, Huu P.
Tuoc, Tran
Emerging Role of m(6) A Methylome in Brain Development: Implications for Neurological Disorders and Potential Treatment
title Emerging Role of m(6) A Methylome in Brain Development: Implications for Neurological Disorders and Potential Treatment
title_full Emerging Role of m(6) A Methylome in Brain Development: Implications for Neurological Disorders and Potential Treatment
title_fullStr Emerging Role of m(6) A Methylome in Brain Development: Implications for Neurological Disorders and Potential Treatment
title_full_unstemmed Emerging Role of m(6) A Methylome in Brain Development: Implications for Neurological Disorders and Potential Treatment
title_short Emerging Role of m(6) A Methylome in Brain Development: Implications for Neurological Disorders and Potential Treatment
title_sort emerging role of m(6) a methylome in brain development: implications for neurological disorders and potential treatment
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170044/
https://www.ncbi.nlm.nih.gov/pubmed/34095121
http://dx.doi.org/10.3389/fcell.2021.656849
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