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A G-tract element in apoptotic agents-induced alternative splicing
Alternative splicing of a single pre-mRNA transcript can produce protein isoforms that promote either cell growth or death. Here we show that Ro-31-8220 (Ro), an apoptotic agent that inhibits protein kinase C and activates the c-Jun N terminal kinase, decreased the proportion of the cell growth-prom...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2425498/ https://www.ncbi.nlm.nih.gov/pubmed/18440980 http://dx.doi.org/10.1093/nar/gkn207 |
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author | Hai, Yan Cao, Wenguang Liu, Guodong Hong, Say-Pham Elela, Sherif Abou Klinck, Roscoe Chu, Jiayou Xie, Jiuyong |
author_facet | Hai, Yan Cao, Wenguang Liu, Guodong Hong, Say-Pham Elela, Sherif Abou Klinck, Roscoe Chu, Jiayou Xie, Jiuyong |
author_sort | Hai, Yan |
collection | PubMed |
description | Alternative splicing of a single pre-mRNA transcript can produce protein isoforms that promote either cell growth or death. Here we show that Ro-31-8220 (Ro), an apoptotic agent that inhibits protein kinase C and activates the c-Jun N terminal kinase, decreased the proportion of the cell growth-promoting Bcl-xL splice variant. Targeted mutagenesis analyses narrowed down a critical sequence to a 16-nt G-tract element (Gt16). Transferring this element to a heterologous gene conferred Ro response on an otherwise constitutive exon. The Ro effect was reduced by okadaic acid, an inhibitor of protein phosphatases PP1 and PP2A, in a concentration-dependent manner. Search in the human genome followed by RT–PCR identified a group of genes that contain similar exonic G-tract elements and are responsive to Ro. Moreover, the Gt16 element also mediates the regulation of alternative splicing by other cell apoptosis-inducers particularly retinoic acid. Therefore, the G-tract element likely plays a role in the apoptotic agents-induced alternative splicing of a group of genes. The functions of these genes imply that this regulation will have impact on cell growth/death. |
format | Text |
id | pubmed-2425498 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-24254982008-06-12 A G-tract element in apoptotic agents-induced alternative splicing Hai, Yan Cao, Wenguang Liu, Guodong Hong, Say-Pham Elela, Sherif Abou Klinck, Roscoe Chu, Jiayou Xie, Jiuyong Nucleic Acids Res RNA Alternative splicing of a single pre-mRNA transcript can produce protein isoforms that promote either cell growth or death. Here we show that Ro-31-8220 (Ro), an apoptotic agent that inhibits protein kinase C and activates the c-Jun N terminal kinase, decreased the proportion of the cell growth-promoting Bcl-xL splice variant. Targeted mutagenesis analyses narrowed down a critical sequence to a 16-nt G-tract element (Gt16). Transferring this element to a heterologous gene conferred Ro response on an otherwise constitutive exon. The Ro effect was reduced by okadaic acid, an inhibitor of protein phosphatases PP1 and PP2A, in a concentration-dependent manner. Search in the human genome followed by RT–PCR identified a group of genes that contain similar exonic G-tract elements and are responsive to Ro. Moreover, the Gt16 element also mediates the regulation of alternative splicing by other cell apoptosis-inducers particularly retinoic acid. Therefore, the G-tract element likely plays a role in the apoptotic agents-induced alternative splicing of a group of genes. The functions of these genes imply that this regulation will have impact on cell growth/death. Oxford University Press 2008-06 2008-04-24 /pmc/articles/PMC2425498/ /pubmed/18440980 http://dx.doi.org/10.1093/nar/gkn207 Text en © 2008 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | RNA Hai, Yan Cao, Wenguang Liu, Guodong Hong, Say-Pham Elela, Sherif Abou Klinck, Roscoe Chu, Jiayou Xie, Jiuyong A G-tract element in apoptotic agents-induced alternative splicing |
title | A G-tract element in apoptotic agents-induced alternative splicing |
title_full | A G-tract element in apoptotic agents-induced alternative splicing |
title_fullStr | A G-tract element in apoptotic agents-induced alternative splicing |
title_full_unstemmed | A G-tract element in apoptotic agents-induced alternative splicing |
title_short | A G-tract element in apoptotic agents-induced alternative splicing |
title_sort | g-tract element in apoptotic agents-induced alternative splicing |
topic | RNA |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2425498/ https://www.ncbi.nlm.nih.gov/pubmed/18440980 http://dx.doi.org/10.1093/nar/gkn207 |
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