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Emerging role of m A RNA methylation in nutritional physiology and metabolism. Wu Jiamin,Frazier Katya,Zhang Jingfei,Gan Zhending,Wang Tian,Zhong Xiang Obesity reviews : an official journal of the International Association for the Study of Obesity N -methyladenine (m A) is the most prevalent type of internal RNA methylation in eukaryotic mRNA and plays critical roles in regulating gene expression for fundamental cellular processes and diverse physiological functions. Recent evidence indicates that m A methylation regulates physiology and metabolism, and m A has been increasingly implicated in a variety of human diseases, including obesity, diabetes, metabolic syndrome and cancer. Conversely, nutrition and diet can modulate or reverse m A methylation patterns on gene expression. In this review, we summarize the recent progress in the study of the m A methylation mechanisms and highlight the crosstalk between m A modification, nutritional physiology and metabolism. 10.1111/obr.12942
N-Methyladenosine Guides mRNA Alternative Translation during Integrated Stress Response. Zhou Jun,Wan Ji,Shu Xin Erica,Mao Yuanhui,Liu Xiao-Min,Yuan Xin,Zhang Xingqian,Hess Martin E,Brüning Jens C,Qian Shu-Bing Molecular cell The integrated stress response (ISR) facilitates cellular adaptation to stress conditions via the common target eIF2α. During ISR, the selective translation of stress-related mRNAs often relies on alternative mechanisms, such as leaky scanning or reinitiation, but the underlying mechanism remains incompletely understood. Here we report that, in response to amino acid starvation, the reinitiation of ATF4 is not only governed by the eIF2α signaling pathway, but is also subjected to regulation by mRNA methylation in the form of N-methyladenosine (mA). While depleting mA demethylases represses ATF4 reinitiation, knocking down mA methyltransferases promotes ATF4 translation. We demonstrate that mA in the 5' UTR controls ribosome scanning and subsequent start codon selection. Global profiling of initiating ribosomes reveals widespread alternative translation events influenced by dynamic mRNA methylation. Consistently, Fto transgenic mice manifest enhanced ATF4 expression, highlighting the critical role of mA in translational regulation of ISR at cellular and organismal levels. 10.1016/j.molcel.2018.01.019
A Review in Research Progress Concerning m6A Methylation and Immunoregulation. Zhang Caiyan,Fu Jinrong,Zhou Yufeng Frontiers in immunology Over 100 types of cellular RNA modifications have been identified in both coding and a variety of non-coding RNAs. N6-methyladenosine (m6A) is the most prevalent and abundant post-transcriptional RNA modification on eukaryote mRNA, and its biological functions are mediated by special binding proteins (i.e., methyltransferases, demethylases, and effectors) that recognize this modification. The presence of m6A on transcripts contributes to diverse fundamental cellular functions, such as pre-mRNA splicing, nuclear transport, stability, translation, and microRNA biogenesis, implying an association with numerous human diseases. This review principally summarizes recent progress in the study of m6A methylation mechanisms and relevant roles they play in immunoregulation. 10.3389/fimmu.2019.00922