Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing.
Here, we present evidence for a specific role of the splicing-related factor TCERG1 in regulating apoptosis in live cells by modulating the alternative splicing of the apoptotic genes Bcl-x and Fas. We show that TCERG1 modulates Bcl-x alternative splicing during apoptosis and its activity in Bcl-x a...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0139812&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850189100350439424 |
|---|---|
| author | Marta Montes Mayte Coiras Soraya Becerra Cristina Moreno-Castro Elena Mateos Jara Majuelos F Javier Oliver Cristina Hernández-Munain José Alcamí Carlos Suñé |
| author_facet | Marta Montes Mayte Coiras Soraya Becerra Cristina Moreno-Castro Elena Mateos Jara Majuelos F Javier Oliver Cristina Hernández-Munain José Alcamí Carlos Suñé |
| author_sort | Marta Montes |
| collection | DOAJ |
| description | Here, we present evidence for a specific role of the splicing-related factor TCERG1 in regulating apoptosis in live cells by modulating the alternative splicing of the apoptotic genes Bcl-x and Fas. We show that TCERG1 modulates Bcl-x alternative splicing during apoptosis and its activity in Bcl-x alternative splicing correlates with the induction of apoptosis, as determined by assessing dead cells, sub-G1-phase cells, annexin-V binding, cell viability, and cleavage of caspase-3 and PARP-1. Furthermore, the effect of TCERG1 on apoptosis involved changes in mitochondrial membrane permeabilization. We also found that depletion of TCERG1 reduces the expression of the activated form of the pro-apoptotic mitochondrial membrane protein Bak, which remains inactive by heterodimerizing with Bcl-xL, preventing the initial step of cytochrome c release in Bak-mediated mitochondrial apoptosis. In addition, we provide evidence that TCERG1 also participates in the death receptor-mediated apoptosis pathway. Interestingly, TCERG1 also modulates Fas/CD95 alternative splicing. We propose that TCERG1 sensitizes a cell to apoptotic agents, thus promoting apoptosis by regulating the alternative splicing of both the Bcl-x and Fas/CD95 genes. Our findings may provide a new link between the control of alternative splicing and the molecular events leading to apoptosis. |
| format | Article |
| id | doaj-art-df90d38a9abd498fb5a7a8f4d76f1230 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-df90d38a9abd498fb5a7a8f4d76f12302025-08-20T02:15:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011010e013981210.1371/journal.pone.0139812Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing.Marta MontesMayte CoirasSoraya BecerraCristina Moreno-CastroElena MateosJara MajuelosF Javier OliverCristina Hernández-MunainJosé AlcamíCarlos SuñéHere, we present evidence for a specific role of the splicing-related factor TCERG1 in regulating apoptosis in live cells by modulating the alternative splicing of the apoptotic genes Bcl-x and Fas. We show that TCERG1 modulates Bcl-x alternative splicing during apoptosis and its activity in Bcl-x alternative splicing correlates with the induction of apoptosis, as determined by assessing dead cells, sub-G1-phase cells, annexin-V binding, cell viability, and cleavage of caspase-3 and PARP-1. Furthermore, the effect of TCERG1 on apoptosis involved changes in mitochondrial membrane permeabilization. We also found that depletion of TCERG1 reduces the expression of the activated form of the pro-apoptotic mitochondrial membrane protein Bak, which remains inactive by heterodimerizing with Bcl-xL, preventing the initial step of cytochrome c release in Bak-mediated mitochondrial apoptosis. In addition, we provide evidence that TCERG1 also participates in the death receptor-mediated apoptosis pathway. Interestingly, TCERG1 also modulates Fas/CD95 alternative splicing. We propose that TCERG1 sensitizes a cell to apoptotic agents, thus promoting apoptosis by regulating the alternative splicing of both the Bcl-x and Fas/CD95 genes. Our findings may provide a new link between the control of alternative splicing and the molecular events leading to apoptosis.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0139812&type=printable |
| spellingShingle | Marta Montes Mayte Coiras Soraya Becerra Cristina Moreno-Castro Elena Mateos Jara Majuelos F Javier Oliver Cristina Hernández-Munain José Alcamí Carlos Suñé Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing. PLoS ONE |
| title | Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing. |
| title_full | Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing. |
| title_fullStr | Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing. |
| title_full_unstemmed | Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing. |
| title_short | Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing. |
| title_sort | functional consequences for apoptosis by transcription elongation regulator 1 tcerg1 mediated bcl x and fas cd95 alternative splicing |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0139812&type=printable |
| work_keys_str_mv | AT martamontes functionalconsequencesforapoptosisbytranscriptionelongationregulator1tcerg1mediatedbclxandfascd95alternativesplicing AT maytecoiras functionalconsequencesforapoptosisbytranscriptionelongationregulator1tcerg1mediatedbclxandfascd95alternativesplicing AT sorayabecerra functionalconsequencesforapoptosisbytranscriptionelongationregulator1tcerg1mediatedbclxandfascd95alternativesplicing AT cristinamorenocastro functionalconsequencesforapoptosisbytranscriptionelongationregulator1tcerg1mediatedbclxandfascd95alternativesplicing AT elenamateos functionalconsequencesforapoptosisbytranscriptionelongationregulator1tcerg1mediatedbclxandfascd95alternativesplicing AT jaramajuelos functionalconsequencesforapoptosisbytranscriptionelongationregulator1tcerg1mediatedbclxandfascd95alternativesplicing AT fjavieroliver functionalconsequencesforapoptosisbytranscriptionelongationregulator1tcerg1mediatedbclxandfascd95alternativesplicing AT cristinahernandezmunain functionalconsequencesforapoptosisbytranscriptionelongationregulator1tcerg1mediatedbclxandfascd95alternativesplicing AT josealcami functionalconsequencesforapoptosisbytranscriptionelongationregulator1tcerg1mediatedbclxandfascd95alternativesplicing AT carlossune functionalconsequencesforapoptosisbytranscriptionelongationregulator1tcerg1mediatedbclxandfascd95alternativesplicing |