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Title:
N6-methyladenosine dynamics in neurodevelopment and aging, and its potential role in Alzheimerās disease | Genome Biology
Description:
Background N6-methyladenosine (m6A) modification is known to impact many aspects of RNA metabolism, including mRNA stability and translation, and is highly prevalent in the brain. Results We show that m6A modification displays temporal and spatial dynamics during neurodevelopment and aging. Genes that are temporally differentially methylated are more prone to have mRNA expression changes and affect many pathways associated with nervous system development. Furthermore, m6A shows a distinct tissue-specific methylation profile, which is most pronounced in the hypothalamus. Tissue-specific methylation is associated with an increase in mRNA expression and is associated with tissue-specific developmental processes. During the aging process, we observe significantly more m6A sites as age increases, in both mouse and human. We show a high level of overlap between mouse and human; however, humans at both young and old ages consistently show more m6A sites compared to mice. Differential m6A sites are found to be enriched in alternative untranslated regions of genes that affect aging-related pathways. These m6A sites are associated with a strong negative effect on mRNA expression. We also show that many Alzheimer-related transcripts exhibit decreased m6A methylation in a mouse model of Alzheimerās disease, which is correlated with reduced protein levels. Conclusions Our results suggest that m6A exerts a critical function in both early and late brain development in a spatio-temporal fashion. Furthermore, m6A controls protein levels of key genes involved in Alzheimerās disease-associated pathways, suggesting that m6A plays an important role in aging and neurodegenerative disease.
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Keywords {š}
pubmed, methylation, article, google, scholar, cas, mrna, genes, rna, levels, brain, compared, weeks, mice, fig, central, expression, transcripts, disease, protein, mouse, aging, alzheimers, methylated, gene, development, utr, differentially, role, file, xfad, wang, neurodevelopment, sites, additional, human, differential, data, zhang, show, regulation, week, analysis, alternative, involved, function, liu, showing, nmethyladenosine, mettl,
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headline:N6-methyladenosine dynamics in neurodevelopment and aging, and its potential role in Alzheimerās disease
description:N6-methyladenosine (m6A) modification is known to impact many aspects of RNA metabolism, including mRNA stability and translation, and is highly prevalent in the brain. We show that m6A modification displays temporal and spatial dynamics during neurodevelopment and aging. Genes that are temporally differentially methylated are more prone to have mRNA expression changes and affect many pathways associated with nervous system development. Furthermore, m6A shows a distinct tissue-specific methylation profile, which is most pronounced in the hypothalamus. Tissue-specific methylation is associated with an increase in mRNA expression and is associated with tissue-specific developmental processes. During the aging process, we observe significantly more m6A sites as age increases, in both mouse and human. We show a high level of overlap between mouse and human; however, humans at both young and old ages consistently show more m6A sites compared to mice. Differential m6A sites are found to be enriched in alternative untranslated regions of genes that affect aging-related pathways. These m6A sites are associated with a strong negative effect on mRNA expression. We also show that many Alzheimer-related transcripts exhibit decreased m6A methylation in a mouse model of Alzheimerās disease, which is correlated with reduced protein levels. Our results suggest that m6A exerts a critical function in both early and late brain development in a spatio-temporal fashion. Furthermore, m6A controls protein levels of key genes involved in Alzheimerās disease-associated pathways, suggesting that m6A plays an important role in aging and neurodegenerative disease.
datePublished:2021-01-05T00:00:00Z
dateModified:2021-01-05T00:00:00Z
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keywords:
Epitranscriptomics
m6A
Neurodevelopment
Aging
Alzheimerās
Regulation of mRNA levels
Regulation of protein levels
Alternative 3ā²UTR
Animal Genetics and Genomics
Human Genetics
Plant Genetics and Genomics
Microbial Genetics and Genomics
Bioinformatics
Evolutionary Biology
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headline:N6-methyladenosine dynamics in neurodevelopment and aging, and its potential role in Alzheimerās disease
description:N6-methyladenosine (m6A) modification is known to impact many aspects of RNA metabolism, including mRNA stability and translation, and is highly prevalent in the brain. We show that m6A modification displays temporal and spatial dynamics during neurodevelopment and aging. Genes that are temporally differentially methylated are more prone to have mRNA expression changes and affect many pathways associated with nervous system development. Furthermore, m6A shows a distinct tissue-specific methylation profile, which is most pronounced in the hypothalamus. Tissue-specific methylation is associated with an increase in mRNA expression and is associated with tissue-specific developmental processes. During the aging process, we observe significantly more m6A sites as age increases, in both mouse and human. We show a high level of overlap between mouse and human; however, humans at both young and old ages consistently show more m6A sites compared to mice. Differential m6A sites are found to be enriched in alternative untranslated regions of genes that affect aging-related pathways. These m6A sites are associated with a strong negative effect on mRNA expression. We also show that many Alzheimer-related transcripts exhibit decreased m6A methylation in a mouse model of Alzheimerās disease, which is correlated with reduced protein levels. Our results suggest that m6A exerts a critical function in both early and late brain development in a spatio-temporal fashion. Furthermore, m6A controls protein levels of key genes involved in Alzheimerās disease-associated pathways, suggesting that m6A plays an important role in aging and neurodegenerative disease.
datePublished:2021-01-05T00:00:00Z
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Epitranscriptomics
m6A
Neurodevelopment
Aging
Alzheimerās
Regulation of mRNA levels
Regulation of protein levels
Alternative 3ā²UTR
Animal Genetics and Genomics
Human Genetics
Plant Genetics and Genomics
Microbial Genetics and Genomics
Bioinformatics
Evolutionary Biology
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