Coordination Funds

过去20年的研究表明，在mRNAs水平上的基因调控与转录调控一样重要。在真核细胞中，mRNAs总是以一种明确的方式与各种RNA结合蛋白结合，形成更高阶的复合体。这些复合体调节用于翻译的文本的时间和空间可用性。它们是高度动态的，在mRNA从转录到降解的过程中，它们的组成发生了变化。一种特殊类型的基于RNA的基因调控是通过分子马达将mRNAs沿着细胞骨架主动运输到细胞外围，在那里它们被局部翻译。这导致了亚细胞蛋白质梯度。信使核糖核酸的定位和翻译广泛存在于真核生物中，在细胞不对称分裂、胚胎发生和神经元可塑性等多种过程中发挥着重要作用。信使核糖核酸转运因子受损与许多遗传性疾病有关，主要是神经性疾病。FOR2333研究单位的目标是将来自德国各地的各种专家聚集在一起，研究信使核糖核酸本地化的不同方面。研究团队由来自广泛专业领域的科学家组成，包括细胞生物学、生物化学、遗传学、结构生物学和生物信息学。在我们的第二个资助期，我们希望了解(I)定位mRNAs中的顺式作用元件是如何定义的，(Ii)一个RNA结合蛋白中的不同结构域是如何协同调节RNA定位的，以及(Iii)当mRNA转运复合体改变其亚细胞位置或环境提示时，为什么以及如何发生重塑。我们将利用我们在第一个资助期建立的强有力的合作关系，在定期的网络会议、方法讲习班和一次国际会议上培训青年科学家。简而言之，这个研究小组汇聚了来自德国各地的初级和高级科学家，以促进我们对mRNA本地化的理解。

Work of the last 20 years demonstrated that gene regulation at the level of mRNAs is as important as transcriptional control. In eukaryotic cells, mRNAs are always associated with various RNA-binding proteins in a well-defined manner, forming higher-order complexes. These complexes regulate the temporal and spatial availability of transcripts for translation. They are highly dynamic and change their composition during the life of an mRNA from transcription to degradation. A special type of RNA-based gene regulation is the active transport of mRNAs by molecular motors along the cytoskeleton to the cell periphery, where they are locally translated. This results in subcellular protein gradients. mRNA localization and localized translation is found throughout eukaryotes and plays a role in diverse processes such as asymmetric cell division, embryogenesis, and neuronal plasticity. Impaired mRNA transport factors have been implicated in a number of heritable, mostly neuronal diseases. The aim of the FOR2333 Research Unit is to bring together various experts from throughout Germany, studying different aspects of mRNA localization. The research team consists of scientists from a broad range of expertise, including cell biology, biochemistry, genetics, structural biology and bioinformatics. In our second funding period, we wish to understand (i) how cis-acting elements within localizing mRNAs are defined, (ii) how different domains within one RNA-binding protein cooperate to mediate RNA localization, and (iii) why and how remodeling of mRNA transport complexes occurs when they change their subcellular location or upon environmental cues. We will make use of our strong collaborative ties, established in the first funding period, to train young scientists at regular network meetings, a method workshop and one international conference. In short, this Research Unit brings together junior and senior scientists from throughout Germany to advance our understanding of mRNA localization.