Evolution of RNA Binding Protein Regulation of Brain Development

基因编码蛋白质，这些蛋白质负责我们看到的各种细胞类型。然而，在基因的表达和最终产生的蛋白质之间有一个关键的中介：信使RNA（mRNA）。mRNA的调节对特定蛋白质产生的时间和位置有巨大影响。mRNA的这种控制是通过一个复杂的转录后基因调控网络来实现的--所有调节从基因表达到蛋白质产生的步骤的各种因素。转录后基因调控网络的组成部分之一是RNA结合蛋白（RBP），即与mRNA结合并控制其在细胞中命运的蛋白质。在发育中的神经系统中，负责制造大脑的神经祖细胞必须产生多种不同类型的细胞。在这些细胞中，RBP作为转录后基因调控网络的一部分，控制某些蛋白质何时何地产生，对外部信号作出反应，使神经祖细胞产生不同的细胞类型。这种转录后调节水平在哺乳动物大脑中得到了很好的表征。然而，在其他脊椎动物（鱼类、两栖动物、爬行动物和鸟类）中，大脑发育的转录后调控鲜为人知。本计画将探讨一种研究较少的脊椎动物溪七鳃鳗（Lampetra planeri）的RBP，它是转录后基因调控网络的主要组成部分。它将专注于参与神经发生（神经元的产生）过程的RBP，并研究编码这些蛋白质的基因的进化历史。它将研究这些RBP在七鳃鳗发育过程中的表达位置和时间，以及它们的功能。本研究将通过比较系统发育的方法阐明脊椎动物神经祖细胞的转录后基因调控网络的进化。BBSRC优先领域：-生物科学的系统方法-数据驱动的生物学-前沿生物科学：理解生命的规则

Genes encode proteins, which are responsible for the various cell types we see. However, there is a crucial intermediary between the expression of a gene and the final protein that is produced: messenger RNA (mRNA). The regulation of mRNA has a massive impact on the time and location a particular protein will be produced. This control of mRNA is achieved by a complex post-transcriptional gene regulatory network - all the various factors that regulate the steps that lead from gene expression to protein production. One of the components of post-transcriptional gene regulatory networks are RNA-binding proteins (RBPs), proteins that bind to the mRNAs and control their fates in the cell. In the developing nervous system, the neural progenitor cells that are responsible for making the brain have to produce a diverse number of different cell types. In these cells, RBPs operate as part of the post-transcriptional gene regulatory network to control when and where certain proteins will be produced, reacting to external signals to allow the neural progenitors to produce the different cell types. This level of post-transcriptional regulation is well characterised in mammalian brains. However, in other vertebrates (fish, amphibians, reptiles and birds), posttranscriptional regulation of brain development is less known. This project will investigate RBPs, a major component of the post-transcriptional gene regulatory network, in a less studied vertebrate, the brook lamprey (Lampetra planeri). It will focus on RBPs that are involved in the process of neurogenesis (the production of neurons) and characterise the evolutionary history of the genes that encode these proteins. It will investigate where and when these RBPs are expressed during the development of the lamprey, as well as their function. This research will shed light on the evolution of the post-transcriptional gene regulatory network underpinning neural progenitor cells in vertebrates by leveraging a comparative phylogenetic approach.BBSRC priority areas: - Systems approaches to the biosciences- Data driven biology- Frontier bioscience: understanding the rules of life