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PreprintCited by 84RNA Research and SplicingRNA and protein synthesis mechanismsRNA regulation and disease

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

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Mabin, Justin W., Woodward, Lauren A., Patton, Robert, Yi, Zhongxia, Jia, Mengxuan, Wysocki, Vicki, Bundschuh, Ralf, Singh, Guramrit·2018·Cell Reports
DOI 10.1101/355495PMC PMC6328047

Preprint — published as 10.1016/j.celrep.2018.11.046

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Abstract

SUMMARY: 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.

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    “Consistently, functionally related groups of genes encoding unstable transcripts (e.g., cell cycle, mRNA processing, and DNA damage; Schwanhäusser et al., 2011) are enriched in CASC3-EJC upon translation inhibition (Figure 5B).”

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Metadata

Authors
Mabin, J. W., Woodward, L. A., Patton, R., Yi, Z., Jia, M., Wysocki, V., Bundschuh, R., & Singh, G.
Affiliations
The Ohio State University (US)
Corresponding author
Singh, Guramrit
ORCID
Venue
Cell Reports
Publisher
openRxiv
Published
2018-06-25
Volume
25
Issue
9
Pages
2431-2446.e7
ISSN
2211-1247 (ISSN-L)
DOI
10.1101/355495
PMC
PMC6328047
OpenAlex
W2963365525
Cited by
84
References
1
Citations by year
2026: 9 · 2025: 11 · 2024: 14 · 2023: 8 · 2022: 14 · 2021: 8 · 2020: 12 · 2019: 6 · 2018: 2
FWCI
2.49
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Ohio State University
  • National Institutes of Health (1s10od023582-01)
  • National Institute of General Medical Sciences (R01GM120209)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
exon junction complex, RNPS1, nonsense-mediated mRNA decay, SR proteins, post-transcriptional regulation, mRNA splicing
MeSH terms
Animals, Cell Nucleus, Exons, HeLa Cells, Humans, Kinetics, Neoplasm Proteins, Protein Binding, Ribonucleoproteins, RNA, Messenger, Protein Biosynthesis, RNA-Binding Proteins, Mice, Hydrodynamics, HEK293 Cells, Nonsense Mediated mRNA Decay

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