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Fusaric 酸诱导肝内全局 m6A RNA 甲基化和 m6A 调控基因的差异表达——一项初步研究。

Fusaric acid induces hepatic global m6A RNA methylation and differential expression of m6A regulatory genes - a pilot study.

机构信息

Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, Howard College Campus, University of KwaZulu-Natal, Durban, South Africa.

出版信息

Epigenetics. 2022 Jun;17(6):695-703. doi: 10.1080/15592294.2021.1975937. Epub 2021 Sep 13.

Abstract

N6-methyladenosine (m6A) is an abundant epitranscriptomic mark that regulates gene expression to execute cellular developmental programmes and environmental adaptation. Fusaric acid (FA) is a mycotoxin that contaminates agricultural foods and exerts toxicity in humans and animals; however, its epitranscriptomic effects are unclear. We investigated the effect of FA on global m6A RNA methylation and mRNA expression levels of key m6A regulatory genes in C57BL/6 mouse livers. C57BL/6 mice ( = 6/group) were orally administered 0.1 M phosphate-buffered saline (PBS) or 50 mg/kg FA. Mice were euthanized 24 h after oral administration, livers were harvested, and RNA was isolated. RNA samples were assayed for global m6A levels using an m6A RNA Methylation Quantification Kit. The mRNA expression of m6A regulators i.e. writers, erasers, and readers were measured by qRT-PCR. FA increased global m6A RNA methylation ( < 0.0001) in mouse livers. FA increased the expression of ( = 0.0143) and ( = 0.0281), and decreased the expression of ( = 0.0036) and ( = 0.0035). The expression of ( = 0.0007), ( = 0.0061), and ( = 0.0258) were increased by FA in mouse livers. This study shows that the liver m6A epitranscriptome can be modified by FA exposure in an model and can be useful for identifying the molecular mechanisms whereby m6A RNA modifications influence the toxicological outcomes of FA exposure.

摘要

N6-甲基腺苷(m6A)是一种丰富的转录后修饰标记,可调节基因表达,以执行细胞发育程序和环境适应。伏马菌素(FA)是一种污染农业食品并在人类和动物中产生毒性的真菌毒素;然而,其转录后修饰效应尚不清楚。我们研究了 FA 对 C57BL/6 小鼠肝脏中全局 m6A RNA 甲基化和关键 m6A 调节基因 mRNA 表达水平的影响。C57BL/6 小鼠(每组 6 只)经口给予 0.1 M 磷酸盐缓冲盐水(PBS)或 50 mg/kg FA。经口给药 24 小时后处死小鼠,采集肝脏并分离 RNA。使用 m6A RNA 甲基化定量试剂盒测定 RNA 样品中的全局 m6A 水平。通过 qRT-PCR 测量 m6A 调节剂(即写入器、擦除器和读取器)的 mRNA 表达。FA 增加了小鼠肝脏中的全局 m6A RNA 甲基化(<0.0001)。FA 增加了 (=0.0143)和 (=0.0281)的表达,并降低了 (=0.0036)和 (=0.0035)的表达。FA 还增加了 (=0.0007)、 (=0.0061)和 (=0.0258)在小鼠肝脏中的表达。这项研究表明,FA 暴露可修饰 模型中的肝脏 m6A 转录后组,并可用于识别 m6A RNA 修饰影响 FA 暴露毒理学结果的分子机制。

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