PT  - JOURNAL ARTICLE
AU  - Justin W. Mabin
AU  - Lauren A. Woodward
AU  - Robert Patton
AU  - Zhongxia Yi
AU  - Mengxuan Jia
AU  - Vicki Wysocki
AU  - Ralf Bundschuh
AU  - Guramrit Singh
TI  - The exon junction complex undergoes a compositional switch that alters mRNP structure and nonsense-mediated mRNA decay activity
AID  - 10.1101/355495
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 355495
4099  - http://biorxiv.org/content/early/2018/06/25/355495.short
4100  - http://biorxiv.org/content/early/2018/06/25/355495.full
AB  - 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.