Distinct pathogenic mechanisms of various RARS1 mutations in Pelizaeus-Merzbacher-like disease

doi:10.1007/s11427-020-1838-2

	Distinct pathogenic mechanisms of various RARS1 mutations in Pelizaeus-Merzbacher-like disease
	Li, Guang 1,2; Eriani, Gilbert 3; Wang, En-Duo1,2,4 ; Zhou, Xiao-Long 1,2
	2021-10
发表期刊	SCIENCE CHINA-LIFE SCIENCES
ISSN	1674-7305
EISSN	1869-1889
卷号	64 期号:10 页码:#VALUE!
DOI	10.1007/s11427-020-1838-2
摘要	Mutations of the genes encoding aminoacyl-tRNA synthetases are highly associated with various central nervous system disorders. Recurrent mutations, including c.5A>G, p.D2G; c.1367C>T, p.S456L; c.1535G>A, p.R512Q and c.1846_1847del, p. Y616Lfs*6 of RARS1 gene, which encodes two forms of human cytoplasmic arginyl-tRNA synthetase (hArgRS), are linked to Pelizaeus-Merzbacher-like disease (PMLD) with unclear pathogenesis. Among these mutations, c.5A>G is the most extensively reported mutation, leading to a p.D2G mutation in the N-terminal extension of the long-form hArgRS. Here, we showed the detrimental effects of R512Q substitution and Delta C mutations on the structure and function of hArgRS, while the most frequent mutation c.5A>G, p.D2G acted in a different manner without impairing hArgRS activity. The nucleotide substitution c.5A>G reduced translation of hArgRS mRNA, and an upstream open reading frame contributed to the suppressed translation of the downstream main ORF. Taken together, our results elucidated distinct pathogenic mechanisms of various RARS1 mutations in PMLD.
关键词	aminoacyl-tRNA synthetase (aaRS) central nervous system (CNS) protein biosynthesis translation initiation tRNA
URL	查看原文
收录类别	SCI ; SCIE
语种	英语
WOS研究方向	Life Sciences & Biomedicine - Other Topics
WOS类目	Biology
WOS记录号	WOS:000613046100001
出版者	SCIENCE PRESS
WOS关键词	TRANSFER-RNA-SYNTHETASE ; AMINOACYL-TRANSFER-RNA ; AUG INITIATOR CODON ; EUKARYOTIC TRANSLATION INITIATION ; RIBONUCLEIC-ACID SYNTHETASE ; SPINAL-CORD INVOLVEMENT ; OPEN READING FRAME ; BRAIN-STEM ; 2 FORMS ; PROTEIN
原始文献类型	Article; Early Access
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/125861
专题	生命科学与技术学院_特聘教授组_王恩多组
通讯作者	Wang, En-Duo; Zhou, Xiao-Long
作者单位	1.Chinese Acad Sci, State Key Lab Mol Biol, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China; 2.Univ Chinese Acad Sci, Shanghai 200031, Peoples R China; 3.Univ Strasbourg, Architecture & React ARN, UPR9002, CNRS,Inst Biol Mol & Cellulaire, F-67084 Strasbourg, France; 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Li, Guang,Eriani, Gilbert,Wang, En-Duo,et al. Distinct pathogenic mechanisms of various RARS1 mutations in Pelizaeus-Merzbacher-like disease[J]. SCIENCE CHINA-LIFE SCIENCES,2021,64(10):#VALUE!.
APA	Li, Guang,Eriani, Gilbert,Wang, En-Duo,&Zhou, Xiao-Long.(2021).Distinct pathogenic mechanisms of various RARS1 mutations in Pelizaeus-Merzbacher-like disease.SCIENCE CHINA-LIFE SCIENCES,64(10),#VALUE!.
MLA	Li, Guang,et al."Distinct pathogenic mechanisms of various RARS1 mutations in Pelizaeus-Merzbacher-like disease".SCIENCE CHINA-LIFE SCIENCES 64.10(2021):#VALUE!.