Analysis of cytoplasmic functions of the exon junction complex

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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.