A global perspective of Exon Junction Complexes in Nonsense-mediated mRNA Decay (NMD)

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Successfully processed mRNAs that reach the cytoplasm are bound by protein complexes at their exon junctions, which are referred to as exon junction complexes (EJC). EJCs are critical components of a molecular machine that controls different modes of cytoplasmic gene regulation including translation, RNA localisation, and control of RNA stability by nonsense mediated decay. Previously, we have established that different classes of mRNAs are targeted by alternative NMD pathways that require different EJC co-factors. Further, we have defined how EJCs are assembled and how the co-factors that are in short supply are recycled. Based on these findings with “model mRNAs”, we will now explore mRNA:EJC interactions at a transcriptomic level. Specifically, we will analyze (1) the co-factor composition of EJCs that bind different classes of mRNAs, (2) the distribution of EJCs on mRNAs and (3) how the composition and the distribution of EJC change upon external stimuli and in different cell types. The project will thus address the fundamental question of how one of the key mechanisms controlling mRNA stability contributes to the cytoplasmic regulation of gene expression on a systemic level.