scholarly journals The Exon Junction Complex Core Represses Caner-specific Mature mRNA Re-splicing: A Potential Key Role in Terminating Splicing

2021 ◽  
Author(s):  
Yuta Otani ◽  
Toshiki Kameyama ◽  
Akila Mayeda
Keyword(s):  
Cancer Cells ◽  
Control Factor ◽  
Exon Junction Complex ◽  
Core Component ◽  
Normal Cells ◽  
Knock Down ◽  
Exon Junction ◽  
Mature Mrna ◽  
Complex Core ◽  
Specific Mrna

AbstractUsing the TSG101 pre-mRNA, we previously discovered cancer-specific re-splicing of mature mRNA that generates aberrant transcripts/proteins. The fact that mRNA is aberrantly re-spliced in various cancer cells implies there must be an important mechanism to prevent deleterious re-splicing on the spliced mRNA in normal cells. We thus postulated that the mRNA re-splicing is controlled by specific repressors and we searched for repressor candidates by siRNA-based screening for mRNA re-splicing activity. We found that knock-down of EIF4A3, which is a core component of the exon junction complex (EJC), significantly promoted mRNA re-splicing. Remarkably, we could recapitulate cancer-specific mRNA re-splicing in normal cells by knock-down of any of the core EJC proteins, EIF4A3, MAGOH or RBM8A (Y14), implicating the EJC core as the repressor of mRNA re-splicing often observed in cancer cells. We propose that the EJC core is a critical mRNA quality control factor to prevent over-splicing of mature mRNA.

scholarly journals The Exon Junction Complex Core Represses Cancer-Specific Mature mRNA Re-Splicing: A Potential Key Role in Terminating Splicing

2021 ◽  
Vol 22 (12) ◽  
pp. 6519
Author(s):  
Yuta Otani ◽  
Ken-ichi Fujita ◽  
Toshiki Kameyama ◽  
Akila Mayeda
Keyword(s):  
Cancer Cells ◽  
Control Factor ◽  
Exon Junction Complex ◽  
Core Component ◽  
Normal Cells ◽  
Knock Down ◽  
Exon Junction ◽  
Mature Mrna ◽  
Complex Core ◽  
Specific Mrna

Using TSG101 pre-mRNA, we previously discovered cancer-specific re-splicing of mature mRNA that generates aberrant transcripts/proteins. The fact that mRNA is aberrantly re-spliced in various cancer cells implies there must be an important mechanism to prevent deleterious re-splicing on the spliced mRNA in normal cells. We thus postulated that mRNA re-splicing is controlled by specific repressors, and we searched for repressor candidates by siRNA-based screening for mRNA re-splicing activity. We found that knock-down of EIF4A3, which is a core component of the exon junction complex (EJC), significantly promoted mRNA re-splicing. Remarkably, we could recapitulate cancer-specific mRNA re-splicing in normal cells by knock-down of any of the core EJC proteins, EIF4A3, MAGOH, or RBM8A (Y14), implicating the EJC core as the repressor of mRNA re-splicing often observed in cancer cells. We propose that the EJC core is a critical mRNA quality control factor to prevent over-splicing of mature mRNA.

scholarly journals Regulation of vertebrate embryogenesis by the exon junction complex core component Eif4a3

2010 ◽  
Vol 239 (7) ◽  
pp. 1977-1987 ◽  
Author(s):  
Tomomi Haremaki ◽  
Jyotsna Sridharan ◽  
Shira Dvora ◽  
Daniel C. Weinstein
Keyword(s):  
Exon Junction Complex ◽  
Core Component ◽  
Exon Junction ◽  
Complex Core

scholarly journals Regulation of vertebrate embryogenesis by the Exon Junction Complex core component Eif4a3

2010 ◽  
Vol 344 (1) ◽  
pp. 508
Author(s):  
Daniel C. Weinstein ◽  
Tomomi Haremaki ◽  
Jyotsna Sridharan ◽  
Shira Dvora
Keyword(s):  
Exon Junction Complex ◽  
Core Component ◽  
Exon Junction ◽  
Complex Core

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 The exon junction complex core factor eIF4A3 is a key regulator of HPV16 gene expression

2021 ◽  
Vol 41 (4) ◽  
Author(s):  
Koceila Meznad ◽  
Philippe Paget-Bailly ◽  
Elise Jacquin ◽  
Anne Peigney ◽  
François Aubin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Exon Junction Complex ◽  
Eukaryotic Translation ◽  
Protein Levels ◽  
Exon Junction ◽  
Complex Core ◽  
Eukaryotic Translation Initiation ◽  
E6 And E7

Abstract High-risk human papillomavirus (hrHPVs), particularly HPV16 and HPV18, are the etiologic factors of ano-genital cancers and some head and neck squamous cell carcinomas (HNSCCs). Viral E6 and E7 oncoproteins, controlled at both transcriptional and post-transcriptional levels, drive hrHPVs-induced carcinogenesis. In the present study, we investigated the implication of the DEAD-box helicase eukaryotic translation initiation factor 4A3 (eIF4A3,) an Exon Junction Complex factor, in the regulation of HPV16 gene expression. Our data revealed that the depletion of the factor eIF4A3 up-regulated E7 oncoprotein levels. We also showed that the inhibition of the nonsense-mediated RNA decay (NMD) pathway, resulted in the up-regulation of E7 at both RNA and protein levels. We therefore proposed that HPV16 transcripts might present different susceptibilities to NMD and that this pathway could play a key role in the levels of expression of these viral oncoproteins during the development of HPV-related cancers.

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.

Sign in / Sign up

Export Citation Format

Share Document