Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders  

作　　者：Helen M.Knight Merve DemirbugenÖz Adriana PerezGrovas-Saltijeral 

机构地区：[1]Division of Cells,Organisms and Molecular Genetics,School of Life Sciences,University of Nottingham,Nottingham,UK [2]Department of Pharmaceutical Toxicology,Faculty of Pharmacy,Ankara University,Ankara,Turkey

出　　处：《Neural Regeneration Research》2024年第6期1256-1261,共6页中国神经再生研究（英文版）

基　　金：funded by Notingham University and the Neuroscience Support Group Charity,UK(to HMK);supported by a CONACYT PhD scholarship;MD?was supported by the Postdoctoral Research Fellowship Program of TUBITAK。

摘　　要：The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric

关 键 词：5-methylcytosine methylation Alzheimer's disease cognitive diseases epitranscriptomics intellectual disability Lewy body diseases N6 adenosine RNA modification 

分 类 号：R749.1[医药卫生—神经病学与精神病学]