携带线粒体tRNA~(Thr) 15943T&gt;C协同12S rRNA1555A&gt;G突变的非综合征性耳聋致病机理的初步研究

doi:10.11844/cjcb.2021.08.0008

科研成果详情

题名	携带线粒体tRNA~(Thr) 15943T>C协同12S rRNA1555A>G突变的非综合征性耳聋致病机理的初步研究
其他题名	Preliminary Study of the Mechanism of Non-Syndromic Hearing Loss Carrying Mitochondrial tRNA~(Thr) 15943T>C and 12S rRNA 1555A>G Mutations
作者	卫梦倩 1,2; 唐霄雯1,2; 高应龙 1,2; 管敏鑫1,2
发表日期	2021
发表期刊	中国细胞生物学学报影响因子和分区
语种	中文
原始文献类型	期刊论文
关键词	非综合征性耳聋突变线粒体tRNA~(Thr) 线粒体tRNA^(Thr)
摘要	该研究通过构建携带线粒体tRNA~(Thr) 15943T>C协同12S rRNA 1555A>G突变(双突变组)的永生化淋巴母细胞系,同时建立仅含12S rRNA 1555A>G突变(单突变组)和正常对照组永生化淋巴母细胞系,探究线粒体tRNA~(Thr) 15943T>C协同12S rRNA 1555A>G突变与耳聋发病的关系,以了解线粒体突变致聋的分子机制。对该家系的临床资料进行分析的结果表明,当包括使用氨基糖苷类抗生素(aminoglycoside antibiotic,AmAn)的药物性耳聋家系成员时,此家系耳聋外显率为26%;当排除用药的耳聋成员时,此家系耳聋外显率是10%;相比之下,已报道的14个m.1555A>G的耳聋家系的平均外显率在用药和未用药的情况下分别仅为13%和6%。利用Northern blot和Western blot分别检测三组细胞中线粒体tRNA和多肽的表达量,结果表明相比于正常对照组,tRNA~(Thr)在双突变组中的表达量显著降低,而在单突变组中的表达量无显著变化,tRNATrp、tRNAAla、tRNATyr、tRNACys和tRNAPro的稳态水平在三组细胞中没有显著性差异;CO_2、CO3和A6在双突变组中的表达量显著降低,而在单突变组中的表达量无显著性差异;其他蛋白多肽在三组细胞中的表达量没有显著差异,说明m.15943T>C突变降低了tRNA~(Thr)的稳态水平,致使线粒体部分多肽表达水平下降,从而影响了线粒体呼吸链复合体的功能和稳定性进而导致了线粒体代谢障碍,提示线粒体tRNA~(Thr) 15943T>C可能与m.1555A>G突变引起的耳聋相关。
其他摘要	This study aims to explore the relationship between mitochondrial tRNA~(Thr) 15943T>C and 12S rRNA 1555A>G mutations and non-syndromic hearing loss,and the molecular mechanism of mitochondrial mutations in deafness.Immortalized lymphoblastic cell lines carrying mitochondrial tRNA~(Thr) 15943T>C and 12S rRNA 1555A>G mutations (double mutation group),the same haplotype (R9) with only 12S rRNA 1555A>G mutation(single mutation group),and a normal control group were established.Analysis of the clinical data of this family showed that when the family members of the drug-induced deafness using AmAn (aminoglycoside antibiotic) were included,the penetrance rate of deafness in this family was 26.3%;when the deaf members who used the medicine were excluded,the penetrance rate of deafness was 10%;in contrast,in the reported 14 deaf families with m.1555A>G,the average penetrance rates were only 13% and 6% separately in the treated and untreated conditions.Northern blot and Western blot separately were used to detect the expression of mitochondrial tRNA and polypeptide.Compared with the normal control group,the steady-state level of tRNA~(Thr) was significantly lower in the double-mutation group,but there was no significant change in the single-mutation group.Meanwhile,there was no significant difference in the steady-state level of other tRNAs in the three groups.The expression of CO_2,CO3,and A6 in the double-mutation group was significantly reduced,but their expression had no significant difference in the single-mutation group.The expression levels of other protein polypeptides had no significant difference in the three groups.The m.15943T>C mutation reduces the steady-state level of tRNA~(Thr).It results in a decrease in the expression of some mitochondrial polypeptides,which affects the function and stability of the mitochondrial respiratory chain complex.Eventually,it leads to mitochondrial metabolism disorders,suggesting that mitochondrial tRNA~(Thr) 15943T>C may be related to the deafness with m.1555A>G.
资助项目	浙江省自然科学基金
ISSN	1674-7666
卷号	43 期号:8 页码:1622-1629
DOI	10.11844/cjcb.2021.08.0008
页数	8
收录类别	CSCD ; 万方 ; ISTIC ; PKU ; 北大核心 ; 维普
学科领域	医药、卫生 ; 耳鼻咽喉科学
URL	查看原文
CSCD记录号	CSCD:7031844
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/98857
专题	检验医学院（生命科学学院、生物学实验教学中心）检验医学院（生命科学学院、生物学实验教学中心）_Attardei线粒体研究院
作者单位	1.温州医科大学检验医学院生命科学学院, 温州, 325035 ; 2.温州医科大学Attardi线粒体生物医学研究院, 温州, 325035
第一作者单位	检验医学院（生命科学学院、生物学实验教学中心）; Attardei线粒体研究院
第一作者的第一单位	检验医学院（生命科学学院、生物学实验教学中心）
推荐引用方式 GB/T 7714	卫梦倩,唐霄雯,高应龙,等. 携带线粒体tRNA~(Thr) 15943T>C协同12S rRNA1555A>G突变的非综合征性耳聋致病机理的初步研究[J]. 中国细胞生物学学报,2021,43(8):1622-1629.
APA	卫梦倩, 唐霄雯, 高应龙, & 管敏鑫. (2021). 携带线粒体tRNA~(Thr) 15943T>C协同12S rRNA1555A>G突变的非综合征性耳聋致病机理的初步研究. 中国细胞生物学学报, 43(8), 1622-1629.
MLA	卫梦倩,et al."携带线粒体tRNA~(Thr) 15943T>C协同12S rRNA1555A>G突变的非综合征性耳聋致病机理的初步研究".中国细胞生物学学报 43.8(2021):1622-1629.