Analysis of cytoplasmic functions of the exon junction complex

后生动物细胞核中含有转录本的内含子剪接导致新生mrna上外显子连接复合物（EJC）的沉积。在细胞质内，EJCs是无义介导的mRNA衰变（NMD）的重要标志，并提高剪接mRNA的翻译效率。这两种效应可能通过EJC和翻译机制的共享组件相互关联。我们之前已经确定了EJC成分BTZ在NMD过程中的关键作用，并希望进一步阐明其NMD激活的机制。我们将描述BTZ调控的靶mrna，并确定调节BTZ NMD功能的相互作用的辅助因子。EJC的翻译刺激功能是由EJC相互作用因子SKAR介导的。mtor依赖性激酶S6K1通过与ejc结合的SKAR的直接蛋白-蛋白相互作用募集，磷酸化mRNP的重要成分，从而刺激结合mRNA的翻译效率。我们的目标是表征参与这一过程的分子机制和EJC成分，并鉴定中心磷酸化的mRNP效应蛋白。总之，这些互补的项目将解决在EJC水平上分子连接的两个重要基因表达过程的机制。

Splicing of intron containing transcripts in the nucleus of metazoan cells leads to the deposition of exon junction complexes (EJC) on the nascent mRNAs. Within the cytoplasm, EJCs are essential marks for nonsense-mediated mRNA decay (NMD) and increase the translation efficiency of spliced mRNAs. Both effects are likely interconnected by shared components of the EJC and the translational machinery. We have previously identified a critical role of the EJC component BTZ during NMD and want to further elucidate its mechanism of NMD activation. We will characterize target mRNAs regulated by BTZ and identify interacting co-factors that regulate BTZ’s NMD function. The translation stimulation function of the EJC is mediated by the EJC interacting factor SKAR. The mTOR-dependent kinase S6K1 is recruited by a direct protein-protein interaction to EJC-bound SKAR, phosphorylates important components of the mRNP and thereby stimulates the translation efficiency of the bound mRNA. We aim to characterize the molecular mechanism and the EJC components involved in this process and to identify central phosphorylated mRNP effector proteins. Together, these complementary projects will address the mechanism of two important gene expression processes that are molecularly linked at the level of the EJC.