アクティブボード・2015年 1月
・・・・・2015年 1月 8日更新・・・・・
研究発表を行った学会;
・第37回日本分子生物学会年会
2014年11月25日〜27日(横浜)
タイトル;Novel roles of centromeric non-coding RNP in regulation of sister chromatid cohesion.
発表者;長 裕紀子 氏
(熊本大学 大学院自然科学研究科 谷研究室)
Abstract;
Human centromere consists of repetitive sequences that generate non-coding RNAs. Satellite I RNA is one of ncRNAs transcribed from centromere. To investigate functions of Sat I RNA, we carried out knockdown of Sat I RNA using anti-sense oligo. Sat I RNA depleted HeLa cells showed the Grape shape phenotype, the abnormal nuclear morphology caused by defects of chromosome segregation. We found that Aurora B, a key factor of chromosome segregation, associates with Sat I RNA. Interestingly, in Sat I RNA depleted cells, Aurora B showed elevated kinase activity and its mis-localization from centromeres. It is suggesting that Sat I RNA regulate chromosome segregation through the control of Aurora B function. Chromosome spread revealed that depletion of Sat I RNA causes defective centromeric cohesion of sister chromatids. To investigate roles of Sat I RNA in this process, we examined proteins associated with Sat I RNA by purification of Sat I RNP and identified RBMX as one of components of Sat I RNP. RBMX is known to associate with protein interact with cohesin. Knockdown of RBMX caused defects in chromosome segregation and chromatid cohesion. Furthermore, RBMX dissociated from chromatin fraction in Sat I RNA depleted cells. Sororin is one of regulators for cohesion. Knockdown of Sororin resulted in abnormal cohesion and defective chromosome segregation. Phosphorylation of Sororin by Aurora B causes dissociation of Sororin from cohesin. We speculated that, in Sat I RNA depleted cells, elevated activity of Aurora B affects function of Sororin to regulate the cohesion. These results suggest that Sat I RNP regulates chromosome segregation through the control of chromatid cohesion.