Role of the Nonsense-Mediated Decay Factor hUpf3 in the Splicing-Dependent Exon-Exon Junction Complex

Science ◽  
2001 ◽  
Vol 293 (5536) ◽  
pp. 1832-1836 ◽  
Author(s):  
V. N. Kim
Keyword(s):  
Exon Junction Complex ◽  
Nonsense Mediated Decay ◽  
Exon Junction ◽  
Decay Factor

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 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 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

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 Exon junction complex proteins bind nascent transcripts independently of pre-mRNA splicing in Drosophila melanogaster

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Subhendu Roy Choudhury ◽  
Anand K Singh ◽  
Tina McLeod ◽  
Marco Blanchette ◽  
Boyun Jang ◽  
...  
Keyword(s):  
Specific Interaction ◽  
Polytene Chromosomes ◽  
Exon Junction Complex ◽  
Exon Junction ◽  
Cell Extracts ◽  
Intronless Genes ◽  
Core Proteins ◽  
Central Protein ◽  
Nascent Transcripts

Although it is currently understood that the exon junction complex (EJC) is recruited on spliced mRNA by a specific interaction between its central protein, eIF4AIII, and splicing factor CWC22, we found that eIF4AIII and the other EJC core proteins Y14 and MAGO bind the nascent transcripts of not only intron-containing but also intronless genes on Drosophila polytene chromosomes. Additionally, Y14 ChIP-seq demonstrates that association with transcribed genes is also splicing-independent in Drosophila S2 cells. The association of the EJC proteins with nascent transcripts does not require CWC22 and that of Y14 and MAGO is independent of eIF4AIII. We also show that eIF4AIII associates with both polysomal and monosomal RNA in S2 cell extracts, whereas Y14 and MAGO fractionate separately. Cumulatively, our data indicate a global role of eIF4AIII in gene expression, which would be independent of Y14 and MAGO, splicing, and of the EJC, as currently understood.

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
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