PROTEIN/RNA INTERACTIONS IN SPLICE SITE SELECTION

剪接位点选择中的蛋白质/RNA 相互作用

• 批准号: 6879123
• 负责人: RUI-MING XU
• 金额: $ 36.44万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6879123
• 关键词: RNA binding protein; RNA splicing; crystallization; heterogeneous nuclear ribonucleoprotein; intermolecular interaction; isomorphous substitution; methionine; nuclear receptors; phosphoproteins; protein structure function; ribosomal proteins; small nuclear ribonucleoproteins; spliceosomes

DESCRIPTION (provided by applicant): Most human genes are interrupted by non-coding sequences known as introns. The nascent transcript must be processed to remove the introns and to join the coding sequence into a contiguous mature mRNA molecule. The human genome project provided an estimate that only 1 to 1.5% of the approximately 3x10/9 base pair (bp) genome is spanned by coding sequences or exons, whereas introns occupy approximately 24% of the genome. It is apparent that the cellular machinery is presented with a formidable task to precisely locate the splice sites within a gene's transcript. Another dimension of complexity is added when certain exon sequences are skipped or included, a phenomenon known as alternative splicing. Alternative splicing occurs in a large number of human genes and it plays important roles in regulating gene expression during development and differentiation. Alternative splicing is also responsible for generating molecular diversity in certain cells, such as neurons. Splicing of pre-mRNA involves an ordered assembly of components, including small nuclear ribonucleoprotein particles (snRNP) and additional protein splicing factors, resulting in the formation of a large 50-60S complex, termed the spliceosome. We are interested in understanding the molecular mechanism of splice site recognition from a structural standpoint. In this proposal, we focus our study on several well characterized human splicing factors that are important for splice site selection, namely, SR proteins, heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and the U2 auxiliary factor (U2AF).

描述（由申请人提供）：大多数人基因都被称为内含子的非编码序列中断。必须处理新生的转录本以去除内含子并将编码序列连接到连续的成熟mRNA分子中。人类基因组项目提供了一个估计，即通过编码序列或外显子跨越大约3x10/9碱基对（BP）基因组的1％至1.5％，而内含子占基因组的24％。显然，蜂窝机械具有一项强大的任务，可以精确地定位基因转录本中的剪接位点。当某些外显子序列跳过或包括某些外显子序列时，添加了复杂性的另一个维度，这种现象称为替代剪接。替代剪接发生在许多人类基因中，并且在调节发展和分化过程中的基因表达中起着重要作用。替代剪接还负责在某些细胞（例如神经元）中产生分子多样性。 前MRNA的剪接涉及组件的有序组装，包括小核核糖核蛋白颗粒（SNRNP）和其他蛋白质剪接因子，从而形成了大型50-60S复合物，称为剪接体。我们有兴趣从结构的角度理解剪接位点识别的分子机制。在此提案中，我们将研究重点放在几个具有良好特征的人类剪接因子上，这些因子对于剪接位点选择很重要，即SR蛋白，异质性核核糖核蛋白A1（HNRNP A1）和U2辅助因子（U2AF）。