The exon junction complex undergoes a compositional switch that alters mRNP structure and nonsense-mediated mRNA decay activity

Bibliographic Details
Title: The exon junction complex undergoes a compositional switch that alters mRNP structure and nonsense-mediated mRNA decay activity
Authors: Mabin, Justin W., Woodward, Lauren A., Patton, Robert, Yi, Zhongxia, Jia, Mengxuan, Wysocki, Vicki, Bundschuh, Ralf, Singh, Guramrit
Publication Year: 2018
Collection: Quantitative Biology
Subject Terms: Quantitative Biology - Genomics
More Details: The exon junction complex (EJC) deposited upstream of mRNA exon junctions shapes structure, composition and fate of spliced mRNA ribonucleoprotein particles (mRNPs). To achieve this, the EJC core nucleates assembly of a dynamic shell of peripheral proteins that function in diverse post-transcriptional processes. To illuminate consequences of EJC composition change, we purified EJCs from human cells via peripheral proteins RNPS1 and CASC3. We show that EJC originates as an SR-rich mega-dalton sized RNP that contains RNPS1 but lacks CASC3. After mRNP export to the cytoplasm and before translation, the EJC undergoes a remarkable compositional and structural remodeling into an SR-devoid monomeric complex that contains CASC3. Surprisingly, RNPS1 is important for nonsense-mediated mRNA decay (NMD) in general whereas CASC3 is needed for NMD of only select mRNAs. The promotion of switch to CASC3-EJC slows down NMD. Overall, the EJC compositional switch dramatically alters mRNP structure and specifies two distinct phases of EJC-dependent NMD.
Document Type: Working Paper
Access URL: http://arxiv.org/abs/1807.00789
Accession Number: edsarx.1807.00789
Database: arXiv
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