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典型文献
Loss of Wtap results in cerebellar ataxia and degeneration of Purkinje cells
文献摘要:
N6-methyladenosine(m6A)modification,which is achieved by the METTL3/METTL14/WTAP methyl-transferase complex,is the most abundant internal mRNA modification.Although recent evidence indicates that m6A can regulate neurodevelopment as well as synaptic function,the roles of m6A modification in the cerebellum and related synaptic connections are not well established.Here,we report that Purkinje cell(PC)-specific WTAP knockout mice display early-onset ataxia concomitant with cerebellar atrophy due to extensive PC degeneration and apoptotic cell death.Loss of Wtap also causes the aberrant degradation of multiple PC synapses.WTAP depletion leads to decreased expression levels of METTL3/14 and reduced m6A methylation in PCs.Moreover,the expression of GFAP and NF-L in the degenerating cerebellum is increased,suggesting severe neuronal injuries.In conclusion,this study demonstrates the critical role of WTAP-mediated m6A modification in cerebellar PCs,thus providing unique insights related to neurode-generative disorders.
文献关键词:
作者姓名:
Yeming Yang;Guo Huang;Xiaoyan Jiang;Xiao Li;Kuanxiang Sun;Yi Shi;Zhenglin Yang;Xianjun Zhu
作者机构:
The Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine,Center for Medical Genetics,Sichuan Provincial People's Hospital,University of Electronic Science and Technology of China,Chengdu,Sichuan 610072,China;Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences(2019RU026),Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital,Chengdu,Sichuan 610072,China;Key Laboratory of Tibetan Medicine Research,Chinese Academy of Sciences and Qinghai Provincial Key Laboratory of Tibetan Medicine Research,Northwest Institute of Plateau Biology,Xining,Qinghai 810008,China
文献出处:
引用格式:
[1]Yeming Yang;Guo Huang;Xiaoyan Jiang;Xiao Li;Kuanxiang Sun;Yi Shi;Zhenglin Yang;Xianjun Zhu-.Loss of Wtap results in cerebellar ataxia and degeneration of Purkinje cells)[J].遗传学报,2022(09):847-858
A类:
Wtap,degenerating,neurode
B类:
Loss,results,cerebellar,ataxia,degeneration,Purkinje,cells,N6,methyladenosine,m6A,modification,which,achieved,by,METTL3,METTL14,WTAP,transferase,complex,most,abundant,internal,Although,recent,evidence,indicates,that,can,regulate,neurodevelopment,well,synaptic,function,roles,cerebellum,related,connections,are,not,established,Here,report,specific,knockout,mice,display,early,onset,concomitant,atrophy,due,extensive,apoptotic,death,also,causes,aberrant,degradation,multiple,synapses,depletion,leads,decreased,expression,levels,reduced,methylation,PCs,Moreover,GFAP,increased,suggesting,severe,neuronal,injuries,In,conclusion,this,study,demonstrates,critical,mediated,thus,providing,unique,insights,generative,disorders
AB值:
0.599669
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