Defining intronic sequences involved in mTOR mRNA splicing and stabilization.

选择性剪接是有助于增强蛋白质多样性的主要机制，它允许估计的 24,000 至 32,000 个蛋白质编码基因与假定合成的超过 80,000 至 100,000 个不同蛋白质之间存在差异。剪接的基础是被称为剪接体的复合体对内含子和外显子的识别，并且被证明受到大量效应物（例如蛋白质和小RNA）的高度调节。我们最近在哺乳动物雷帕霉素靶标 (mTOR) mRNA 中发现了关键的调控序列，该序列会引发翻译过早终止，从而导致 mTOR 蛋白（细胞完整性的主要调节因子）的截短版本。这个新的 NSERC 研究计划的总体目标是了解这些 mRNA 序列如何调节 mTOR 表达并识别含有这些内含子序列的其他 mRNA。通过定义 mTOR 剪接和表达的调节机制，我们期望评估这些内含子序列是否是调节 mRNA 表达和参与细胞完整性不同方面的蛋白质稳定性的一般机制的重要方面。

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.