ElciRNA 和 ASAT siRNA功能机理研究
发布时间：2019-05-09 09:36
【摘要】：第一部分：RNAi干扰途径在各种生命活动中起着重要的调控作用。然而,在哺乳动物的有丝分裂过程中,RNAi干扰途径是否参与染色体分离的问题至今还没有定论。在本文中,我们发现两个RNAi干扰途径的关键因子(Dicer和AG02)直接参与调控染色体分离步骤。降低Dicer和AG02的表达水平会导致高比率的染色体分离滞后现象,而且这个效应不依赖于miRNA通路。另外,我们还发现α-satellite RNA是人类中期染色体上的重要组成成分。过量积累在染色体上的α-satellite RNA会干扰着丝粒和动粒的形成与功能。进一步的研究结果表明,Dicer和AG02通过调控α-satellite RNA在中期染色体上的水平和分布,从而保证CENPC1正确定位到着丝粒区域,最终确保有丝分裂时期的染色体可以正确分离。我们的研究成果阐明了哺乳动物中RNAi干扰通路在染色体分离中的功能以及功能机理,为RNAi干扰途径的功能研究提供了崭新的视角,为将来相关的科研目标提供了新的方向。第二部分：非编码RNA是生命活动中的关键调控因子。近几年,科学家在人类和鼠类细胞中发现了一类具有封闭环状结构的环状RNA,其中两个环状RNA定位于细胞质中,扮演着miRNA海绵的角色,调控细胞质中miRNA的水平含量。在本文中,我们发现了一类与RNA聚合酶II相结合的环状RNA(Exon-intron circular RNA, EIciRNA)。EIciRNA包含内含子序列,而且它们的侧翼互补序列可以促进它们的形成。另外,我们还发现EIciRNA通过RNA-RNA相互作用与U1 snRNP结合形成U1 snRNP-EIciRNA复合物,该复合体会与Pol Ⅱ复合体结合,进而调控亲本基因的转录效率。本文阐明了EIciRNA顺式调控亲本基因转录的分子机理,为基因表达调控这个庞大的研究领域提供了崭新的思考角度。
[Abstract]:The first part: RNAi interference pathway plays an important role in the regulation of various life activities. However, whether the RNAi interference pathway is involved in chromosome segregation in mammalian mitosis is still uncertain. In this paper, we found that two key factors of RNAi interference pathway (Dicer and AG02) are directly involved in the regulation of chromosome segregation. Decreasing the expression level of Dicer and AG02 leads to a high rate of chromosome segregation lag, and this effect is independent of the miRNA pathway. In addition, we also found that 伪-satellite RNA is an important component of human metaphase chromosomes. Excessive accumulation of 伪-satellite RNA on chromosomes interferes with the formation and function of centromere and megasome. The further results showed that Dicer and AG02 regulated the level and distribution of 伪-satellite RNA on metaphase chromosomes, thus ensuring that CENPC1 was correctly located in the centromeric region and finally the chromosomes at mitotic stage could be separated correctly. Our research results clarify the function and mechanism of RNAi interference pathway in chromosome segregation in mammals, and provide a new perspective for the functional study of RNAi interference pathway, and provide a new direction for the related scientific research objectives in the future. The second part: non-coding RNA is the key regulatory factor in life activities. In recent years, scientists have found a class of circular RNA, with closed circular structure in human and mouse cells, two of which are located in cytoplasm and play the role of miRNA sponge, which regulates the level of miRNA in cytoplasm. In this paper, we found that a class of cyclic RNA (Exon-intron circular RNA, EIciRNA). EII) RNA combined with RNA polymerase II contains intron sequences, and their flanking complementary sequences can promote their formation. In addition, we also found that EIciRNA binds U1-snRNP through RNA-RNA interaction to form U1-snRNP-EIciRNA complex, which binds to Pol 鈪，
本文编号：2472668
[Abstract]:The first part: RNAi interference pathway plays an important role in the regulation of various life activities. However, whether the RNAi interference pathway is involved in chromosome segregation in mammalian mitosis is still uncertain. In this paper, we found that two key factors of RNAi interference pathway (Dicer and AG02) are directly involved in the regulation of chromosome segregation. Decreasing the expression level of Dicer and AG02 leads to a high rate of chromosome segregation lag, and this effect is independent of the miRNA pathway. In addition, we also found that 伪-satellite RNA is an important component of human metaphase chromosomes. Excessive accumulation of 伪-satellite RNA on chromosomes interferes with the formation and function of centromere and megasome. The further results showed that Dicer and AG02 regulated the level and distribution of 伪-satellite RNA on metaphase chromosomes, thus ensuring that CENPC1 was correctly located in the centromeric region and finally the chromosomes at mitotic stage could be separated correctly. Our research results clarify the function and mechanism of RNAi interference pathway in chromosome segregation in mammals, and provide a new perspective for the functional study of RNAi interference pathway, and provide a new direction for the related scientific research objectives in the future. The second part: non-coding RNA is the key regulatory factor in life activities. In recent years, scientists have found a class of circular RNA, with closed circular structure in human and mouse cells, two of which are located in cytoplasm and play the role of miRNA sponge, which regulates the level of miRNA in cytoplasm. In this paper, we found that a class of cyclic RNA (Exon-intron circular RNA, EIciRNA). EII) RNA combined with RNA polymerase II contains intron sequences, and their flanking complementary sequences can promote their formation. In addition, we also found that EIciRNA binds U1-snRNP through RNA-RNA interaction to form U1-snRNP-EIciRNA complex, which binds to Pol 鈪，
本文编号：2472668
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