选择性剪接对基因功能和蛋白结构影响的研究

发布时间：2019-06-18 20:08

【摘要】：选择性剪接事件是真核生物的一种基本而重要的调控机制。通过不同的剪接方式,剪接获得的基因序列可以组合产生多种不同的mRNA剪接异构体。这些mRNA剪接异构体被翻译成不同结构的蛋白产物或是功能相互拮抗的蛋白产物。鉴于表达水平的不同,在同一细胞中产生不同的表型。选择性剪接事件的发生为仅拥有20000～25000个基因的人类执行了复杂的生理功能,因此,对选择性剪接事件的研究有助于揭示人类机体的功能机制,认识人类生命的本质。基因承载着决定生物性状的遗传信息,蛋白质是生物机体内功能的执行者。基因序列决定蛋白质的氨基酸序列,蛋白质的氨基酸序列决定蛋白质的结构,蛋白质的结构状态决定蛋白质的功能。由此可见,基因与蛋白质的结构和功能之间具有一脉相承的关系。基因序列的变化将影响着蛋白质的序列组成,进而影响着蛋白质的结构和功能。选择性剪接事件的发生能够改变基因序列,也就意味着会对蛋白质的结构和功能产生重要的影响。从这个角度出发,本课题着重分析选择性剪接事件对基因功能以及产物蛋白结构的影响。具体从以下四个方面进行研究:(1)鉴于选择性剪接事件发生的不确定性,分析选择性剪接事件发生的有效性。首先,在MISO数据库中获取所有的选择性剪接事件数据,鉴于选择性剪接事件的不确定性,根据判断选择性剪接事件数据有效性的规则,对选择性剪接事件数据进行分析与处理,最后,提取所有符合判别规则的选择性剪接事件数据,并用做本文后续研究的实验数据。(2)分析发生选择性剪接事件的基因功能。首先,根据选择性剪接事件注释信息获取基因序列的信息,依据选择性剪接事件对基因编码子的影响程度,将选择性剪接事件划分为两类:改变原有编码框的选择性剪接事件Ⅰ类和保留原有编码框的选择性剪接事件Ⅱ类,然后利用GO,对发生选择性剪接事件的基因进行功能分析,分析两类剪事件中基因的功能类别。分析结果表明,两类剪接事件具有最多的基因功能是酶的催化作用,其次是连接功能,最少的是通路调控。此外,对比改变和保留原有编码框的选择性剪接事件发现基因功能并没有明显差异。(3)构建选择性剪接事件中基因序列到氨基酸序列的翻译模型。三个核苷酸能够编码一个氨基酸,基因与蛋白质之间存在着生物密码子表。本文首先分析现有翻译软件在翻译选择性剪接事件的基因序列中存在的问题,然后针对选择性剪接事件的特点,提出基因序列翻译成氨基酸序列的规则,最后根据翻译规则,将选择性剪接事件中基因序列翻译成氨基酸序列。从翻译模型得出的结果,共翻译出39541条氨基酸序列。(4)分析选择性剪接事件对其产物蛋白结构的影响。本文利用VSL2无序蛋白结构预测模型,预测选择性剪接事件中蛋白产物的无序结构,同时也预测了无序区域的长度。预测结果显示,选择性剪接会使产物蛋白具有无序结构的倾向性。
[Abstract]:Alternative splicing events are a basic and important regulatory mechanism of eukaryotes. By different splicing methods, the gene sequences obtained by splicing can be combined to produce a variety of different mRNA splice isoforms. These mRNA splice isoforms are translated into protein products of different structures or functionally antagonistic protein products. In view of the differences in the level of expression, different phenotypes are produced in the same cell. The occurrence of alternative splicing events is a complex physiological function for humans with only 20000-25000 genes, so the study of alternative splicing events can help to reveal the human body's functional mechanism and recognize the nature of human life. The gene carries the genetic information that determines the biological character, and the protein is the performer of the function in the biological body. The gene sequence determines the amino acid sequence of the protein, the amino acid sequence of the protein determines the structure of the protein, the structural state of the protein determines the function of the protein. Thus, there is a relationship between the structure and function of the gene and the protein. The change of the gene sequence will affect the sequence composition of the protein, thus affecting the structure and function of the protein. The occurrence of a selective splicing event can change the sequence of genes, which means an important effect on the structure and function of the protein. From this point of view, this subject focuses on the analysis of the effects of alternative splicing events on gene function and product protein structure. The study was carried out in the following four aspects: (1) the effectiveness of the selective splicing event was analyzed in view of the uncertainty of the selective splicing event. first, all the alternative splicing event data is obtained in the MISO database, and in view of the uncertainty of the selective splicing event, the selective splicing event data is analyzed and processed according to the rules for judging the validity of the selective splicing event data, and finally, All the alternative splicing event data in accordance with the criteria for discrimination were extracted and the experimental data for subsequent studies in this paper were used. (2) The gene function of the selective splicing event was analyzed. first, according to the information of the selective splicing event annotation information to obtain the gene sequence, the selective splicing event is divided into two types according to the degree of the effect of the selective splicing event on the gene coding sub-; The selective splicing event type I of the original coding frame and the selective splicing event type II of the original coding frame are changed, and then the function of the gene in the two types of scissors events is analyzed by using the GO and the function analysis of the gene which has the selective splicing event. The results of the analysis show that the two types of splicing events have the most gene function as the catalytic action of the enzyme, the second is the connection function, and the least is the pathway regulation. In addition, there was no significant difference in the gene function compared to the alternative splicing events that alter and retain the original coding frame. (3) constructing a translation model of a gene sequence in a selective splicing event to an amino acid sequence. The three nucleonic acid can encode an amino acid, and there is a biological codon table between the gene and the protein. In this paper, the problems of the existing translation software in the translation of alternative splicing events are analyzed, and then the rules for the translation of the gene sequence into the amino acid sequence are put forward according to the characteristics of the selective splicing event, and finally, according to the translation rule, The gene sequence in a selective splicing event is translated into an amino acid sequence. A total of 39541 amino acid sequences were translated from the results of the translation model. (4) The effect of alternative splicing events on its product protein structure was analyzed. In this paper, the unordered structure of the protein product in the selective splicing event is predicted by using the VSL2 disorder protein structure prediction model, and the length of the disorder region is also predicted. The results of the prediction show that alternative splicing can lead to the tendency of the product protein to have a disordered structure.
【学位授予单位】：哈尔滨工程大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：Q78

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