生物
N6-甲基腺苷
信使核糖核酸
甲基化
非翻译区
基因
基因表达
翻译(生物学)
阿尔茨海默病
人脑
基因表达调控
翻译效率
遗传学
疾病
神经科学
内科学
甲基转移酶
医学
作者
Andrew M. Shafik,Feiran Zhang,Zhiqin Guo,Qing Dai,Kinga Pajdzik,Yangping Li,Yunhee Kang,Bing Yao,Hao Wu,Chuan He,Emily G. Allen,Ranhui Duan,Peng Jin
出处
期刊:Genome Biology
[Springer Nature]
日期:2021-01-05
卷期号:22 (1)
被引量:137
标识
DOI:10.1186/s13059-020-02249-z
摘要
Abstract Background N6-methyladenosine (m 6 A) 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 m 6 A 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, m 6 A 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 m 6 A 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 m 6 A sites compared to mice. Differential m 6 A sites are found to be enriched in alternative untranslated regions of genes that affect aging-related pathways. These m 6 A sites are associated with a strong negative effect on mRNA expression. We also show that many Alzheimer-related transcripts exhibit decreased m 6 A methylation in a mouse model of Alzheimer’s disease, which is correlated with reduced protein levels. Conclusions Our results suggest that m 6 A exerts a critical function in both early and late brain development in a spatio-temporal fashion. Furthermore, m 6 A controls protein levels of key genes involved in Alzheimer’s disease-associated pathways, suggesting that m 6 A plays an important role in aging and neurodegenerative disease.
科研通智能强力驱动
Strongly Powered by AbleSci AI