PROTEIN/RNA INTERACTIONS IN SPLICE SITE SELECTION

大多数真核基因都被内含子打断。 主 转录本必须被处理以去除内含子并加入 将编码序列插入连续的mRNA分子中。 不同mRNA 分子可以由相同的前mRNA通过替代的方法产生， 当前体mRNA含有多个内含子时进行剪接。的先决条件 从核前mRNA中精确切除内含子是特异性 正确的5'和3'位点的识别和配对。 蜂窝 执行这一高度管制的过程的机器涉及一个有序的 组件的组装，包括异质核 核糖核蛋白，小核核糖核颗粒和额外的 蛋白质因子，称为剪接因子。 这座大型建筑群 作为剪接体。 蛋白质-RNA相互作用是一种重要的机制 在剪接体组装和调节可变剪接中， 已知在控制基因表达中起重要作用， 发展差异化。 我们将研究 通过剪接因子和hnRNP的序列特异性蛋白质-RNA相互作用 蛋白质的组成性和选择性前mRNA剪接。 我们 这项研究将有助于理解这些剪接体是如何 组分在调节前体mRNA剪接中实现其功能， 原子水平。

Most eukaryotic genes are interrupted by introns. The primary transcript must be processed to remove the introns and to join the coding sequence into a contiguous mRNA molecule. Different mRNA molecules can be generated from the same pre-mRNA by alternative splicing when the pre-mRNA contains multiple introns. A prerequisite for the accurate excision of introns from nuclear pre-mRNA is specific recognition and pairing of the correct 5' and 3' sites. Cellular machinery carrying out this highly regulated process involves an ordered assembly of components, including heterogeneous nuclear ribonucleoproteins, small nuclear ribonuclear particles and additional protein factors, known as splicing factors. This large complex is known as the spliceosome. Protein-RNA interaction is an essential mechanism in spliceosome assembly and in regulating alternative splicing, which is known to play an important role in controlling gene expressing during development an differentiation. We will study the structural basis of sequence-specific protein-RNA interactions by splicing factors and hnRNP proteins in both constitutive and alternative pre-mRNA splicing. Our study will lead to the understanding of how these spliceosomal components achieve their function in regulating pre-mRNA splicing at an atomic level.