![]() How long mRNPs exist in their compact states and when, Eventually, the mRNA within mRNPs must be unpacked to allow access Through the nuclear pore, and transport within the cytoplasm to arrive at its site Structure may facilitate mRNP navigation of the intranuclear environment, export These complexes is packaged into an overall compact mRNP structure. Leading to 150-to 200-nt-long RNA footprints, suggesting that the RNA polymer within These stable mega-RNPs ensheath RNA well beyond the canonical EJC deposition site, Mega-dalton-sized RNPs ( Singh et al., 2012). We previously showed that, within spliced mRNPs, EJCs interact with oneĪnother as well as with several SR and SR-like proteins to assemble into ![]() Vary between mRNPs leading to compositionally distinct mRNPs, an idea that has Share similar functions and yet may act on different mRNAs e.g., RNPS1 and CASC3Ĭan both enhance NMD but may have distinct mRNA targets ( Gehring et al., 2005). Proteins (e.g., the TREX complex), translation factors (e.g., SKAR), and NMD factors Proteins such as pre-mRNA splicing factors (e.g., SRm160, RNPS1), mRNA export Nonetheless, the stable EJC core interacts with a dynamic shell of peripheral EJC May not be necessary for all EJC functions ( Mao et However, more recent evidence suggests that CASC3 may not be present in all EJCs and Or Barentsz) to form a stable tetrameric core ( Boehm Trimeric core is thought to be joined by a fourth protein CASC3 (also known as MLN51 RNA-bound EIF4A3 is locked in place by RBM8A (also known as Y14) and MAGOH. ![]() If an EJC remainsīound to an mRNA downstream of a ribosome terminating translation, it stimulates MRNA export, mRNA transport and localization, and translation. Gene expression at several post-transcriptional steps, including pre-mRNA splicing, Junctions ( Boehm and Gehring, 2016 Le Hir et al., 2016 Woodward et al., 2017). Which assembles during pre-mRNA splicing 24 nucleotides (nt) upstream of exon-exon When, where, and how the multitude of mRNP components changeĭuring its lifetime and how such changes impact mRNP function remain largelyĪ key component of all spliced mRNPs is the exon junction complex (EJC), Metabolic pathways, and the nuclear cap and poly(A)-tail binding proteins areĮxchanged for their cytoplasmic counterparts after mRNP export to promote For example, mRNAĮxport adapters are removed upon mRNP export to provide directionality to mRNP However, the understanding of mechanisms and consequences of mRNP compositionĬhange remains confined to only a handful of its components. The vast proteinĬomplement of mRNPs has been illuminated ( Hentze etĪl., 2018) and is presumed to change as mRNPs progress through their (mRNAs) exist decorated with proteins as mRNA-protein particles, or mRNPs ( Singh et al., 2015). Overall, the EJC compositional switch dramaticallyĪlters mRNP structure and specifies two distinct phases of EJC-dependentįrom the time of their birth until their eventual demise, messenger RNAs In general, whereas CASC3 is needed for NMD of only select mRNAs. Surprisingly, RNPS1 is important for nonsense-mediated mRNA decay (NMD) Sometime before or during translation, the EJC undergoes compositionalĪnd structural remodeling into an SR-devoid monomeric complex that containsĬASC3. We show that theĮJC originates as an SR-rich mega-dalton-sized RNP that contains RNPS1 but lacksĬASC3. To illuminate consequences of EJC composition change, we purifiedĮJCs from human cells via peripheral proteins RNPS1 and CASC3. Shell of peripheral proteins that function in diverse post-transcriptional To achieve this, the EJC core nucleates assembly of a dynamic Shapes structure, composition, and fate of spliced mRNA ribonucleoprotein The exon junction complex (EJC) deposited upstream of mRNA exon junctions
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