Defining intronic sequences involved in mTOR mRNA splicing and stabilization.

选择性剪接是促进蛋白质多样性增强的主要机制，这种机制允许估计24,000至32,000个蛋白质编码基因之间的差异，以及假设合成的80,000至100,000个不同蛋白质之间的差异。剪接的基础是被称为剪接体的复杂的剪接体识别内含子和外显子，并被证明受到大量效应物的高度调控，如蛋白质和小RNA。我们最近在哺乳动物靶标雷帕霉素(MTOR)mRNA中发现了关键的调控序列，导致提前翻译终止，导致mTOR蛋白的截短版本，mTOR蛋白是细胞完整性的主要调节因子。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的表达，并识别其他含有这些内含子序列的mRNA。通过定义调控mTOR剪接和表达的机制，我们期望评估这些内含子序列是否是调控参与细胞完整性不同方面的蛋白质的mRNA表达和稳定性的一般机制的关键方面。

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.