Dysregulated mitochondrial and cytosolic tRNA m1A methylation in Alzheimer's disease.
Dysregulated mitochondrial and cytosolic tRNA m1A methylation in Alzheimer's disease.
复制标题
阿尔茨海默病中线粒体和胞质 tRNA m1A 甲基化失调。
DOI：
10.1093/hmg/ddab357
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发表时间：
2022
影响因子：
3.5
通讯作者：
Jin,Peng
中科院分区：
文献类型：
--
作者：
Shafik,AndrewM;Zhou,Huiqing;Lim,Junghwa;Dickinson,Bryan;Jin,Peng
RNA modifications affect many aspects of RNA metabolism and are involved in the regulation of many different biological processes. Mono-methylation of adenosine in the N1 position, N1-methyladensoine (m1A), is a reversible modification that is known to target rRNAs and tRNAs. m1A has been shown to increase tRNA structural stability and induce correct tRNA folding. Recent studies have begun to associate the dysregulation of epitranscriptomic control with age-related disorders such as Alzheimer’s disease. Here, we applied the newly developed m1A-quant-seq approach to map the brain abundant m1A RNA modification in the cortex of an Alzheimer’s disease mouse model, 5XFAD. We observed hypomethylation in both mitochondrial and cytosolic tRNAs in 5XFAD mice compared with wild type. Furthermore, the main enzymes responsible for the addition of m1A in mitochondrial (TRMT10C, HSD17B10) and cytosolic tRNAs (TRMT61A) displayed decreased expression in 5XFAD compared with wild-type mice. Knockdown of these enzymes results in a more severe phenotype in aDrosophilatau model, and differential m1A methylation is correlated with differences in mature mitochondrial tRNA expression. Collectively, this work suggests that hypo m1A modification in tRNAs may play a role in Alzheimer’s disease pathogenesis.
