eIF4AIII binds spliced mRNA in the exon junction complex and is essential for nonsense-mediated decay

2004 ◽  
Vol 11 (4) ◽  
pp. 346-351 ◽  
Author(s):  
Toshiharu Shibuya ◽  
Thomas Ø Tange ◽  
Nahum Sonenberg ◽  
Melissa J Moore
Keyword(s):  
Exon Junction Complex ◽  
Nonsense Mediated Decay ◽  
Exon Junction

scholarly journals Identification of antiviral roles for the exon–junction complex and nonsense-mediated decay in flaviviral infection

2019 ◽  
Vol 4 (6) ◽  
pp. 985-995 ◽  
Author(s):  
Minghua Li ◽  
Jeffrey R. Johnson ◽  
Billy Truong ◽  
Grace Kim ◽  
Nathan Weinbren ◽  
...  
Keyword(s):  
Exon Junction Complex ◽  
Nonsense Mediated Decay ◽  
Exon Junction

scholarly journals CASC3 promotes transcriptome-wide activation of nonsense-mediated decay by the exon junction complex

2020 ◽  
Vol 48 (15) ◽  
pp. 8626-8644 ◽  
Author(s):  
Jennifer V Gerbracht ◽  
Volker Boehm ◽  
Thiago Britto-Borges ◽  
Sebastian Kallabis ◽  
Janica L Wiederstein ◽  
...  
Keyword(s):  
Exon Junction Complex ◽  
Core Component ◽  
Mrna Isoforms ◽  
Nonsense Mediated Decay ◽  
Exon Junction ◽  
Endonucleolytic Cleavage ◽  
Core Proteins ◽  
Messenger Ribonucleoprotein ◽  
Cytoplasmic Processes

Abstract The exon junction complex (EJC) is an essential constituent and regulator of spliced messenger ribonucleoprotein particles (mRNPs) in metazoans. As a core component of the EJC, CASC3 was described to be pivotal for EJC-dependent nuclear and cytoplasmic processes. However, recent evidence suggests that CASC3 functions differently from other EJC core proteins. Here, we have established human CASC3 knockout cell lines to elucidate the cellular role of CASC3. In the knockout cells, overall EJC composition and EJC-dependent splicing are unchanged. A transcriptome-wide analysis reveals that hundreds of mRNA isoforms targeted by nonsense-mediated decay (NMD) are upregulated. Mechanistically, recruiting CASC3 to reporter mRNAs by direct tethering or via binding to the EJC stimulates mRNA decay and endonucleolytic cleavage at the termination codon. Building on existing EJC-NMD models, we propose that CASC3 equips the EJC with the persisting ability to communicate with the NMD machinery in the cytoplasm. Collectively, our results characterize CASC3 as a peripheral EJC protein that tailors the transcriptome by promoting the degradation of EJC-dependent NMD substrates.

scholarly journals Communication with the Exon-Junction Complex and Activation of Nonsense-Mediated Decay by Human Upf Proteins Occur in the Cytoplasm

2007 ◽  
Vol 27 (5) ◽  
pp. 780-792 ◽  
Author(s):  
Guramrit Singh ◽  
Steffen Jakob ◽  
Mark G. Kleedehn ◽  
Jens Lykke-Andersen
Keyword(s):  
Exon Junction Complex ◽  
Nonsense Mediated Decay ◽  
Exon Junction

scholarly journals The abundance of RNPS1, a protein component of the exon junction complex, can determine the variability in efficiency of the Nonsense Mediated Decay pathway

2007 ◽  
Vol 35 (13) ◽  
pp. 4542-4551 ◽  
Author(s):  
Marcelo H. Viegas ◽  
Niels H. Gehring ◽  
Stephen Breit ◽  
Matthias W. Hentze ◽  
Andreas E. Kulozik
Keyword(s):  
Protein Component ◽  
Exon Junction Complex ◽  
Nonsense Mediated Decay ◽  
Exon Junction

scholarly journals CASC3 promotes transcriptome-wide activation of nonsense-mediated decay by the exon junction complex

2019 ◽  
Author(s):  
Jennifer V. Gerbracht ◽  
Volker Boehm ◽  
Thiago Britto-Borges ◽  
Sebastian Kallabis ◽  
Janica L. Wiederstein ◽  
...  
Keyword(s):  
Exon Junction Complex ◽  
Core Component ◽  
Mrna Isoforms ◽  
Nonsense Mediated Decay ◽  
Exon Junction ◽  
Endonucleolytic Cleavage ◽  
Core Proteins ◽  
Messenger Ribonucleoprotein ◽  
Cytoplasmic Processes

AbstractThe exon junction complex (EJC) is an essential constituent and regulator of spliced messenger ribonucleoprotein particles (mRNPs) in metazoans. As a core component of the EJC, CASC3 was described to be pivotal for EJC-dependent nuclear and cytoplasmic processes. However, recent evidence suggests that CASC3 functions differently from other EJC core proteins. Here, we have established human CASC3 knockout cell lines to elucidate the cellular role of CASC3. In the knockout cells, overall EJC composition and EJC-dependent splicing are unchanged. A transcriptome-wide analysis reveals that hundreds of mRNA isoforms targeted by nonsense-mediated decay (NMD) are upregulated. Mechanistically, recruiting CASC3 to reporter mRNAs by direct tethering or via binding to the EJC stimulates mRNA decay and endonucleolytic cleavage at the termination codon. Building on existing EJC-NMD models, we propose that CASC3 equips the EJC with the ability to communicate with the NMD machinery in the cytoplasm. Collectively, our results characterize CASC3 as a peripheral EJC protein that tailors the transcriptome by promoting the degradation of EJC-dependent NMD substrates.

scholarly journals The exon-junction complex helicase eIF4A3 controls cell fate via coordinated regulation of ribosome biogenesis and translational output

2021 ◽  
Vol 7 (32) ◽  
pp. eabf7561
Author(s):  
Dimitris C. Kanellis ◽  
Jaime A. Espinoza ◽  
Asimina Zisi ◽  
Elpidoforos Sakkas ◽  
Jirina Bartkova ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Ribosome Biogenesis ◽  
Small Subunit ◽  
Initiation Factor ◽  
Exon Junction Complex ◽  
Cell Cycle Regulators ◽  
Nonsense Mediated Decay ◽  
Exon Junction ◽  
Cancer Pathogenesis

Eukaryotic initiation factor 4A-III (eIF4A3), a core helicase component of the exon junction complex, is essential for splicing, mRNA trafficking, and nonsense-mediated decay processes emerging as targets in cancer therapy. Here, we unravel eIF4A3’s tumor-promoting function by demonstrating its role in ribosome biogenesis (RiBi) and p53 (de)regulation. Mechanistically, eIF4A3 resides in nucleoli within the small subunit processome and regulates rRNA processing via R-loop clearance. EIF4A3 depletion induces cell cycle arrest through impaired RiBi checkpoint–mediated p53 induction and reprogrammed translation of cell cycle regulators. Multilevel omics analysis following eIF4A3 depletion pinpoints pathways of cell death regulation and translation of alternative mouse double minute homolog 2 (MDM2) transcript isoforms that control p53. EIF4A3 expression and subnuclear localization among clinical cancer specimens correlate with the RiBi status rendering eIF4A3 an exploitable vulnerability in high-RiBi tumors. We propose a concept of eIF4A3’s unexpected role in RiBi, with implications for cancer pathogenesis and treatment.

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