Target cis elements of the RNA-binding protein Arid5a in inflammatory cytokine-based diseases (B16*)

在发育和免疫反应过程中，严格控制基因表达尤为重要。转录后基因调控包括对信使核糖核酸稳定性的控制和基因产物的翻译。MRNAs在其3‘-非翻译区含有顺式调控元件，这些元件是RNA结合蛋白(RBP)的靶标，并随后决定转录本的命运。在这种背景下，例如，对信使核糖核酸的降解已经研究了二十年。我们将研究新的RBP Arid5a及其在稳定中的作用，即上调编码参与免疫反应中细胞因子产生的蛋白质的靶mRNAs水平。我们将定义Arid5a的目标顺式元件，并获得RNA-蛋白质复合体的原子分辨图像，这将揭示基于Arid5a的基因调控机制及其在细胞因子基础疾病中的作用。

Tight control of gene expression is particularly important during development and immune response. The post-transcriptional gene regulation comprises the control over mRNA stability and their translation into gene products. mRNAs harbor cis-regulatory elements in their 3´- untranslated regions that are targeted by RNA-binding proteins (RBPs) and subsequently decide about the transcript fate. In this context, mRNA degradation, e.g., has already been studied for two decades. We will investigate the novel RBP Arid5a and its role in stabilizing, i.e. up-regulating levels of target mRNAs coding for proteins involved in cytokine production during immune responses. We will define target cis elements of Arid5a and obtain atom-resolved pictures of RNA-protein complexes that will reveal mechanisms of Arid5a-based gene regulation and its role in cytokine-based diseases.