Regulation of pre-mRNA and mRNA processing by the neuron-specific Hu RNA-binding proteins

神经元特异性 Hu RNA 结合蛋白对前 mRNA 和 mRNA 加工的调节

• 批准号: nhmrc : 349540
• 负责人: Dr Kirk Jensen
• 金额: $ 31.86万
• 依托单位: The University of Adelaide
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/regulation-pre-mrna-binding-proteins/80826
• 关键词: Regulation; pre; mRNA; processing; neuron

The precise control of protein expression is absolutely critical in biology, and the key decisions about which genes are turned on or off at any one moment control the proper growth and maturation of an organism during development, and are responsible for the organism's homeostasis and proper response to environmental changes as an adult. Many gene expression programs are highly complex and controlled by regulating the activation of individual genes as they are copied from DNA to RNA. However, this activation is just the start of the process to produce an active protein. In higher organisms, these RNA copies almost always contain interruptions called introns, which must be excised from the RNA. Also, protein factors bound to specific RNAs can dictate whether the RNA is used to make protein or not, and these factors can also affect the localisation of the RNA to a specific sub-cellular destination, giving rise to highly localised protein expression. Evidence suggests that neurons are a cell type that rely heavily on mechanisms of RNA regulation. During development neurons become highly polarised, acquiring an axon which can elongate and find distant synaptic targets. While much is known about how axon growth cones respond to various guidance cues, the mechanisms by which the axon is able to translate this guidance cue information into structural changes which allow the growth cone to expand or collapse is largely unexplored. Recent evidence suggests that accurate growth cone guidance is absolutely dependent upon local protein synthesis. The functional corollary of this finding is that axon guidance requires RNA localisation and control of protein synthesis of RNAs in the growth cone. This phenomenon of spatial gene regulation within an individual cell is a central research interest for understanding how the brain functions.

蛋白质表达的精确控制在生物学中是绝对关键的，在任何一个时刻打开或关闭哪些基因的关键决定控制着生物体在发育过程中的适当生长和成熟，并负责生物体的稳态和对成年环境变化的适当反应。许多基因表达程序非常复杂，并且通过调节单个基因从DNA复制到RNA时的激活来控制。然而，这种激活只是产生活性蛋白质过程的开始。在高等生物中，这些RNA拷贝几乎总是包含称为内含子的中断，必须从RNA中切除。此外，与特定RNA结合的蛋白质因子可以决定RNA是否用于制造蛋白质，并且这些因子还可以影响RNA定位到特定的亚细胞目的地，从而引起高度定位的蛋白质表达。有证据表明，神经元是一种严重依赖RNA调节机制的细胞类型。在发育过程中，神经元变得高度极化，获得可以伸长并找到远处突触靶点的轴突。虽然关于轴突生长锥如何响应各种指导线索的了解很多，但轴突能够将这种指导线索信息转化为允许生长锥扩张或塌陷的结构变化的机制在很大程度上未被探索。最近的证据表明，准确的生长锥的指导是绝对依赖于当地的蛋白质合成。这一发现的功能推论是轴突的指导需要RNA定位和控制生长锥中RNA的蛋白质合成。这种在单个细胞内进行空间基因调控的现象是理解大脑功能的核心研究兴趣。