RING protein 213(RNF213),the susceptibility gene for Moyamoya disease(MMD),possesses two active AAA+ATPase(ATPases Associated with diverse cellular Activities)modules,a RING,and RNF213-ZNFX1 finger(RZ finger)domains.S...RING protein 213(RNF213),the susceptibility gene for Moyamoya disease(MMD),possesses two active AAA+ATPase(ATPases Associated with diverse cellular Activities)modules,a RING,and RNF213-ZNFX1 finger(RZ finger)domains.Several RNF213 variants have been reported in MMD patients,including the p.R4810K variant(rs112735431),which is a founder polymorphism associated with MMDin EastAsia.To elucidate the function of RNF213 and its variant,we investigated the localization of RNF213 and the R4810K variant in this study.RNF213 induced circular hole structures near the nucleus,similar to lipid droplets(LDs),in U-2 OS cells.The holes decorated with tagged RNF213 protein were colocalized with mCherry-RAB5A and mCherry-peroxisome,but not mCherry-RAB9A and other organelles.RNF213 decorated the holes,and the structures were growing and changing to cylindrical objects,but not the R4810K variant efficiently.Furthermore,both AAA+ATPase modules and the ubiquitin ligase domain of RNF213 were required for the formation of the hole structures and cylindrical objects.These findings suggest that RNF213 activity may be involved in the formation of organelle-like structures,and this structure formation by RNF213 may be responsible for vascular functions.展开更多
目的探讨环指蛋白213（RNF213）基因P．R4810K（G〉A）单核苷酸多态性与中国汉族缺血性卒中的关系。方法纳入2013年6月～2013年12月入住郑州大学第一附属医院神经内科汉族缺血性脑卒中患者，所有患者均行血管影像学检查，包括磁共振血...目的探讨环指蛋白213（RNF213）基因P．R4810K（G〉A）单核苷酸多态性与中国汉族缺血性卒中的关系。方法纳入2013年6月～2013年12月入住郑州大学第一附属医院神经内科汉族缺血性脑卒中患者，所有患者均行血管影像学检查，包括磁共振血管成像（MRA）或者CT血管成像（CTA），分为颅内大动脉狭窄或闭塞亚组（intracranial major artery stenosis／occlusion，ICASO）及无颅内大动脉狭窄或闭塞亚组（norl-ICASO），同时选取性别、年龄与缺血性脑卒中组相匹配的健康汉族人为对照组。通过聚合酶链式反应及直接测序方法行多态性位点分析。结果共纳入285例中国汉族缺血性脑卒中患者，其中139例（48．8％）存在不同程度颅内动脉狭窄或者闭塞，146例（51．2％）无颅内大动脉狭窄或闭塞。RNF213基因P．R4810K多态性在缺血性卒中组、1CASO亚组、非ICASO亚组、正常对照组的发生率分别为0．35％（1／285）、0．72％（1／139）、0（0／146）、0．33％（1／300）。和对照组相比，RNF213基因P．R4810K多态性与缺血性卒中组差异无统计学意义（P=1，oddsratio[OR]1．053，95％confi-denceinterval[CI]0．066-16．912），与合并颅内大动脉狭窄或者闭塞亚组问差异同样无统计学意义（P=0．533，OR2．167，95％CI0．135-34．894）。结论RNF213基因P．R4810K单核苷酸多态性与中国汉族缺血性脑卒中及存在ICASO的缺血性脑卒中患者的易患性无相关性，但需在较大样本中进一步验证。展开更多
基金supported by grants(#15611607)from the Ministry of Education,Culture,Sports,Science and Technology of Japan to T.H.
文摘RING protein 213(RNF213),the susceptibility gene for Moyamoya disease(MMD),possesses two active AAA+ATPase(ATPases Associated with diverse cellular Activities)modules,a RING,and RNF213-ZNFX1 finger(RZ finger)domains.Several RNF213 variants have been reported in MMD patients,including the p.R4810K variant(rs112735431),which is a founder polymorphism associated with MMDin EastAsia.To elucidate the function of RNF213 and its variant,we investigated the localization of RNF213 and the R4810K variant in this study.RNF213 induced circular hole structures near the nucleus,similar to lipid droplets(LDs),in U-2 OS cells.The holes decorated with tagged RNF213 protein were colocalized with mCherry-RAB5A and mCherry-peroxisome,but not mCherry-RAB9A and other organelles.RNF213 decorated the holes,and the structures were growing and changing to cylindrical objects,but not the R4810K variant efficiently.Furthermore,both AAA+ATPase modules and the ubiquitin ligase domain of RNF213 were required for the formation of the hole structures and cylindrical objects.These findings suggest that RNF213 activity may be involved in the formation of organelle-like structures,and this structure formation by RNF213 may be responsible for vascular functions.
文摘目的探讨环指蛋白213（RNF213）基因P．R4810K（G〉A）单核苷酸多态性与中国汉族缺血性卒中的关系。方法纳入2013年6月～2013年12月入住郑州大学第一附属医院神经内科汉族缺血性脑卒中患者，所有患者均行血管影像学检查，包括磁共振血管成像（MRA）或者CT血管成像（CTA），分为颅内大动脉狭窄或闭塞亚组（intracranial major artery stenosis／occlusion，ICASO）及无颅内大动脉狭窄或闭塞亚组（norl-ICASO），同时选取性别、年龄与缺血性脑卒中组相匹配的健康汉族人为对照组。通过聚合酶链式反应及直接测序方法行多态性位点分析。结果共纳入285例中国汉族缺血性脑卒中患者，其中139例（48．8％）存在不同程度颅内动脉狭窄或者闭塞，146例（51．2％）无颅内大动脉狭窄或闭塞。RNF213基因P．R4810K多态性在缺血性卒中组、1CASO亚组、非ICASO亚组、正常对照组的发生率分别为0．35％（1／285）、0．72％（1／139）、0（0／146）、0．33％（1／300）。和对照组相比，RNF213基因P．R4810K多态性与缺血性卒中组差异无统计学意义（P=1，oddsratio[OR]1．053，95％confi-denceinterval[CI]0．066-16．912），与合并颅内大动脉狭窄或者闭塞亚组问差异同样无统计学意义（P=0．533，OR2．167，95％CI0．135-34．894）。结论RNF213基因P．R4810K单核苷酸多态性与中国汉族缺血性脑卒中及存在ICASO的缺血性脑卒中患者的易患性无相关性，但需在较大样本中进一步验证。
