The Exon Junction Complex Undergoes a Compositional Switch that Alters mRNP Structure and Nonsense-Mediated mRNA Decay Activity.

Autor:	Mabin JW; Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA., Woodward LA; Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA., Patton RD; Department of Physics, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA., Yi Z; Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA., Jia M; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA., Wysocki VH; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA., Bundschuh R; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA; Department of Physics, The Ohio State University, Columbus, OH 43210, USA; Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA., Singh G; Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA. Electronic address: singh.734@osu.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2018 Nov 27; Vol. 25 (9), pp. 2431-2446.e7. Date of Electronic Publication: 2018 Nov 19.
DOI:	10.1016/j.celrep.2018.11.046
Abstrakt:	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 the EJC originates as an SR-rich mega-dalton-sized RNP that contains RNPS1 but lacks CASC3. Sometime before or during translation, the EJC undergoes 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 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. (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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