Cargando…
CD28 Costimulation Regulates Genome-Wide Effects on Alternative Splicing
CD28 is the major costimulatory receptor required for activation of naïve T cells, yet CD28 costimulation affects the expression level of surprisingly few genes over those altered by TCR stimulation alone. Alternate splicing of genes adds diversity to the proteome and contributes to tissue-specific...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386953/ https://www.ncbi.nlm.nih.gov/pubmed/22768209 http://dx.doi.org/10.1371/journal.pone.0040032 |
_version_ | 1782237041381081088 |
---|---|
author | Butte, Manish J. Lee, Sun Jung Jesneck, Jonathan Keir, Mary E. Haining, W. Nicholas Sharpe, Arlene H. |
author_facet | Butte, Manish J. Lee, Sun Jung Jesneck, Jonathan Keir, Mary E. Haining, W. Nicholas Sharpe, Arlene H. |
author_sort | Butte, Manish J. |
collection | PubMed |
description | CD28 is the major costimulatory receptor required for activation of naïve T cells, yet CD28 costimulation affects the expression level of surprisingly few genes over those altered by TCR stimulation alone. Alternate splicing of genes adds diversity to the proteome and contributes to tissue-specific regulation of genes. Here we demonstrate that CD28 costimulation leads to major changes in alternative splicing during activation of naïve T cells, beyond the effects of TCR alone. CD28 costimulation affected many more genes through modulation of alternate splicing than by modulation of transcription. Different families of biological processes are over-represented among genes alternatively spliced in response to CD28 costimulation compared to those genes whose transcription is altered, suggesting that alternative splicing regulates distinct biological effects. Moreover, genes dependent upon hnRNPLL, a global regulator of splicing in activated T cells, were enriched in T cells activated through TCR plus CD28 as compared to TCR alone. We show that hnRNPLL expression is dependent on CD28 signaling, providing a mechanism by which CD28 can regulate splicing in T cells and insight into how hnRNPLL can influence signal-induced alternative splicing in T cells. The effects of CD28 on alternative splicing provide a newly appreciated means by which CD28 can regulate T cell responses. |
format | Online Article Text |
id | pubmed-3386953 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33869532012-07-05 CD28 Costimulation Regulates Genome-Wide Effects on Alternative Splicing Butte, Manish J. Lee, Sun Jung Jesneck, Jonathan Keir, Mary E. Haining, W. Nicholas Sharpe, Arlene H. PLoS One Research Article CD28 is the major costimulatory receptor required for activation of naïve T cells, yet CD28 costimulation affects the expression level of surprisingly few genes over those altered by TCR stimulation alone. Alternate splicing of genes adds diversity to the proteome and contributes to tissue-specific regulation of genes. Here we demonstrate that CD28 costimulation leads to major changes in alternative splicing during activation of naïve T cells, beyond the effects of TCR alone. CD28 costimulation affected many more genes through modulation of alternate splicing than by modulation of transcription. Different families of biological processes are over-represented among genes alternatively spliced in response to CD28 costimulation compared to those genes whose transcription is altered, suggesting that alternative splicing regulates distinct biological effects. Moreover, genes dependent upon hnRNPLL, a global regulator of splicing in activated T cells, were enriched in T cells activated through TCR plus CD28 as compared to TCR alone. We show that hnRNPLL expression is dependent on CD28 signaling, providing a mechanism by which CD28 can regulate splicing in T cells and insight into how hnRNPLL can influence signal-induced alternative splicing in T cells. The effects of CD28 on alternative splicing provide a newly appreciated means by which CD28 can regulate T cell responses. Public Library of Science 2012-06-29 /pmc/articles/PMC3386953/ /pubmed/22768209 http://dx.doi.org/10.1371/journal.pone.0040032 Text en Butte et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Butte, Manish J. Lee, Sun Jung Jesneck, Jonathan Keir, Mary E. Haining, W. Nicholas Sharpe, Arlene H. CD28 Costimulation Regulates Genome-Wide Effects on Alternative Splicing |
title | CD28 Costimulation Regulates Genome-Wide Effects on Alternative Splicing |
title_full | CD28 Costimulation Regulates Genome-Wide Effects on Alternative Splicing |
title_fullStr | CD28 Costimulation Regulates Genome-Wide Effects on Alternative Splicing |
title_full_unstemmed | CD28 Costimulation Regulates Genome-Wide Effects on Alternative Splicing |
title_short | CD28 Costimulation Regulates Genome-Wide Effects on Alternative Splicing |
title_sort | cd28 costimulation regulates genome-wide effects on alternative splicing |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386953/ https://www.ncbi.nlm.nih.gov/pubmed/22768209 http://dx.doi.org/10.1371/journal.pone.0040032 |
work_keys_str_mv | AT buttemanishj cd28costimulationregulatesgenomewideeffectsonalternativesplicing AT leesunjung cd28costimulationregulatesgenomewideeffectsonalternativesplicing AT jesneckjonathan cd28costimulationregulatesgenomewideeffectsonalternativesplicing AT keirmarye cd28costimulationregulatesgenomewideeffectsonalternativesplicing AT hainingwnicholas cd28costimulationregulatesgenomewideeffectsonalternativesplicing AT sharpearleneh cd28costimulationregulatesgenomewideeffectsonalternativesplicing |