中文版 | English
题名

C9ORF114 调控28S rRNA 甲基化修饰影响 核糖体生成的分子机制研究

其他题名
Molecular mechanism of C9ORF114 in regulating ribosome biogenesis by mediating methylation of 28S rRNA
姓名
姓名拼音
XIONG Minggang
学号
12032632
学位类型
硕士
学位专业
071010 生物化学与分子生物学
学科门类/专业学位类别
07 理学
导师
陈浩
导师单位
人类细胞生物和遗传学系
论文答辩日期
2023-05-08
论文提交日期
2023-07-05
学位授予单位
南方科技大学
学位授予地点
深圳
摘要

核糖体的生物发生是细胞内能量的主要消耗之一,并控制细胞中的其他生物合成活动。这些生物合成的过程需要与细胞周期进程紧密协调,并且同时翻译机器的加倍对细胞的连续增殖来说是至关重要的一环。

最近的研究揭示了核糖体合成与细胞周期调节之间有趣的联系,但其潜在机制在很大程度上仍然难以捉摸。C9ORF114,也被称为SPOUT1,是人类基因组中假定的SPOUT家族1号甲基转移酶,以前被认为是着丝粒相关蛋白,它是中期染色体对齐和中心体与双极纺锤体两极的关联所必需的。然而在此项研究中,我们进一步表明 C9ORF114 同时也是核糖体的生物发生和组成60S核糖体大亚基的关键蛋白。我们通过前期实验发现C9ORF114的亚细胞定位再细胞核的核仁内,并在此基础上通过进一步实验结果验证出C9ORF114会结合到核糖体28S rRNA并与核糖体60S 大亚基形成复合物,从而参与调控细胞翻译过程。在哺乳动物细胞中,C9ORF114 的缺失会损害细胞整体的翻译水平并且影响pre-rRNA 加工,因为没有足够的翻译机器支撑,细胞无法越过细胞周期中的 G1 期到 S 期的检查点,从而无法完成整个细胞周期并表现出细胞增殖的抑制。有趣的是,裂殖酵母中C9ORF114同源基因的KO菌株在氧化应激下表现出生长缺陷,而在正常条件下无明显差异。

综上所述,我们的研究揭示了C9ORF114 为代表的rRNA甲基转移酶在核糖体生物合成中的重要功能,并且同时在进化的角度上论证了蛋白进化的保守性和进化过程中演变出的功能差异,并揭示了 RNA 修饰与细胞周期调节之间的新联系。

关键词
语种
中文
培养类别
独立培养
入学年份
2020
学位授予年份
2023-06
参考文献列表

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生物学
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条目标识符http://sustech.caswiz.com/handle/2SGJ60CL/545094
专题南方科技大学医学院
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熊铭港. C9ORF114 调控28S rRNA 甲基化修饰影响 核糖体生成的分子机制研究[D]. 深圳. 南方科技大学,2023.
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