Defining intronic sequences involved in mTOR mRNA splicing and stabilization.

定义参与 mTOR mRNA 剪接和稳定的内含子序列。

• 批准号: 402880-2012
• 负责人: Huot, MarcEtienne
• 金额: $ 2.19万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=573372
• 关键词: Defining; intronic; sequences; involved; mTOR

Alternative splicing is a major mechanism contributing to the enhancement of protein diversity that allow the discrepancy between the estimated 24,000 to 32,000 protein-coding genes to more than 80,000 to 100,000 different proteins that are postulated to be synthesized. The basis of splicing is the recognition of introns and exons by a complex termed spliceosome and was shown to highly modulated by a plethora of effectors such as protein and small RNA. We recently identified key regulatory sequences within the mammalian target of rapamycin (mTOR) mRNA provoking a premature translational termination that results in a truncated version of the mTOR protein, a major regulator of cellular integrity. The general goal of this new NSERC research program is to understand how these mRNA sequences can regulate mTOR expression and identify other mRNA harboring these intronic sequences. By defining the mechanisms by which mTOR splicing and expression is regulated, we expect to assess whether these intronic sequences are an essential aspect of a general mechanism regulating mRNA expression and stability for protein involved in different aspect of cellular integrity.

选择性剪接是一种主要的机制，有助于增强蛋白质的多样性，使估计的24，000至32，000个蛋白质编码基因之间的差异超过80，000至100，000个不同的蛋白质，假设要合成。剪接的基础是内含子和外显子被称为剪接体的复合物识别，并且被证明受到大量效应物如蛋白质和小RNA的高度调节。我们最近确定了哺乳动物雷帕霉素靶蛋白（mTOR）mRNA中的关键调控序列，该序列引起过早的翻译终止，导致mTOR蛋白的截短版本，这是细胞完整性的主要调节因子。这项新的NSERC研究计划的总体目标是了解这些mRNA序列如何调节mTOR表达，并鉴定含有这些内含子序列的其他mRNA。通过定义mTOR剪接和表达调节的机制，我们期望评估这些内含子序列是否是调节mRNA表达和蛋白质稳定性的一般机制的重要方面，所述蛋白质涉及细胞完整性的不同方面。