Connections between mRNP Composition and mRNA Fate

Abstract

Throughout their lifetime, messenger RNAs (mRNA) exist decorated with proteins as mRNA‐protein particles, or mRNPs. A key component of all spliced mRNPs is the exon junction complex (EJC), which assembles during pre‐mRNA splicing ~24 nucleotides (nt) upstream of exon‐exon junctions. The stable EJC core thus assembled serves as an interaction platform for peripheral proteins that direct mRNA export, localization, translation and nonsense‐mediated mRNA decay (NMD). Both mRNPs and EJCs and are widely presumed to be "dynamic" entities that change during an mRNAs lifetime. We recently discovered that EJCs, and hence spliced mRNPs, undergo an extensive compositional overhaul after their export to cytoplasm. This compositional switch has important implications for the EJC‐dependent NMD pathway, which can now be divided into at least two distinct phases. We find that two compositionally distinct EJCs differentially associate with the NMD factor UPF3B, which is also a peripheral EJC factor that is required for efficient NMD of only a small subset of mRNAs. We will discuss new insights gained from our work into the mechanism of EJC‐dependent NMD in the absence of UPF3B, and about the function of UPF3B in NMD. Overall, our work is shedding new light on how mRNP composition specifies distinct phases or branches of the NMD pathway, an essential post‐transcriptional mechanism that controls cellular adaptation, differentiation and development.Support or Funding InformationThis work is supported by NIH (R01 GM120209). ZY is supported by graduate fellowships from Pelotonia and OSU Center for RNA Biology.