Post-translation regulation of small RNA-guided gene silencing pathways (B03/B04)

MicroRNA(MiRNA)介导的基因沉默是几乎所有细胞途径的中心过程，因此在许多疾病中都会受到影响。MiRNAs引导ArgAerte(AGO)和TNRC6蛋白到靶mRNA上的互补位置，导致基因沉默。这一过程被嵌入到扩展的调控网络中，包括蛋白质相互作用分子以及翻译后修饰途径。在项目B3中，我们将研究影响基因沉默的信号通路，并从功能上表征AGO和TNRC6的蛋白质相互作用伙伴，这是我们在之前的资助期确定的。我们已经建立了生化纯化策略来分离含有AGO和TNRC6的mRNA复合体。这将被进一步优化，并用于低温电子显微镜的结构研究。

MicroRNA (miRNA)-guided gene silencing is a central process in almost all cellular pathways and therefore affected in many diseases. MiRNAs guide Argonaute (Ago) and TNRC6 proteins to complementary sites on target mRNA leading to gene silencing. This process is embedded into extended regulatory networks including protein interactors as well as post-translational modification pathways. In project B3, we will investigate signaling pathways that affect gene silencing and functionally characterize protein interaction partners of Ago and TNRC6, which we have identified during the pervious funding period. We have already established biochemical purification strategies to isolate Ago- and TNRC6-containg mRNA complex. This will be further optimized and used for structural studies using cryo-electron-microscopy.