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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...

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Autores principales: Butte, Manish J., Lee, Sun Jung, Jesneck, Jonathan, Keir, Mary E., Haining, W. Nicholas, Sharpe, Arlene H.
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
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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.
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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
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