  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.
