Accumulation of splice variants and transcripts in response to PI3K inhibition in T cells

 

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dc.contributor.author Riedel, Alice en_ZA
dc.contributor.author Mofolo, Boitumelo en_ZA
dc.contributor.author Avota, Elita en_ZA
dc.contributor.author Schneider-Schaulies, Sibylle en_ZA
dc.contributor.author Meintjes, Ayton en_ZA
dc.contributor.author Mulder, Nicola en_ZA
dc.contributor.author Kneitz, Susanne en_ZA
dc.date.accessioned 2015-12-28T06:47:22Z
dc.date.available 2015-12-28T06:47:22Z
dc.date.issued 2013 en_ZA
dc.identifier.citation Riedel, A., Mofolo, B., Avota, E., Schneider-Schaulies, S., Meintjes, A., Mulder, N., & Kneitz, S. (2013). Accumulation of splice variants and transcripts in response to PI3K inhibition in T cells. PloS one, 8(2). doi:10.1371/journal.pone.0050695 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/16024
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0050695
dc.description.abstract BACKGROUND: Measles virus (MV) causes T cell suppression by interference with phosphatidylinositol-3-kinase (PI3K) activation. We previously found that this interference affected the activity of splice regulatory proteins and a T cell inhibitory protein isoform was produced from an alternatively spliced pre-mRNA. Hypothesis Differentially regulated and alternatively splice variant transcripts accumulating in response to PI3K abrogation in T cells potentially encode proteins involved in T cell silencing. METHODS: To test this hypothesis at the cellular level, we performed a Human Exon 1.0 ST Array on RNAs isolated from T cells stimulated only or stimulated after PI3K inhibition. We developed a simple algorithm based on a splicing index to detect genes that undergo alternative splicing (AS) or are differentially regulated (RG) upon T cell suppression. RESULTS: Applying our algorithm to the data, 9% of the genes were assigned as AS, while only 3% were attributed to RG. Though there are overlaps, AS and RG genes differed with regard to functional regulation, and were found to be enriched in different functional groups. AS genes targeted extracellular matrix (ECM)-receptor interaction and focal adhesion pathways, while RG genes were mainly enriched in cytokine-receptor interaction and Jak-STAT. When combined, AS/RG dependent alterations targeted pathways essential for T cell receptor signaling, cytoskeletal dynamics and cell cycle entry. CONCLUSIONS: PI3K abrogation interferes with key T cell activation processes through both differential expression and alternative splicing, which together actively contribute to T cell suppression. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights 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 credited. en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other T cells en_ZA
dc.subject.other Gene regulation en_ZA
dc.subject.other Alternative splicing en_ZA
dc.subject.other Measles virus en_ZA
dc.subject.other T cell receptors en_ZA
dc.subject.other Reverse transcriptase-polymerase chain reaction en_ZA
dc.subject.other TCR signaling cascade en_ZA
dc.subject.other Cell cycle and cell division en_ZA
dc.title Accumulation of splice variants and transcripts in response to PI3K inhibition in T cells en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2013 Riedel et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Institute of Infectious Disease and Molecular Medicine en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Riedel, A., Mofolo, B., Avota, E., Schneider-Schaulies, S., Meintjes, A., Mulder, N., & Kneitz, S. (2013). Accumulation of splice variants and transcripts in response to PI3K inhibition in T cells. <i>PLoS One</i>, http://hdl.handle.net/11427/16024 en_ZA
dc.identifier.chicagocitation Riedel, Alice, Boitumelo Mofolo, Elita Avota, Sibylle Schneider-Schaulies, Ayton Meintjes, Nicola Mulder, and Susanne Kneitz "Accumulation of splice variants and transcripts in response to PI3K inhibition in T cells." <i>PLoS One</i> (2013) http://hdl.handle.net/11427/16024 en_ZA
dc.identifier.vancouvercitation Riedel A, Mofolo B, Avota E, Schneider-Schaulies S, Meintjes A, Mulder N, et al. Accumulation of splice variants and transcripts in response to PI3K inhibition in T cells. PLoS One. 2013; http://hdl.handle.net/11427/16024. en_ZA
dc.identifier.ris TY - Journal Article AU - Riedel, Alice AU - Mofolo, Boitumelo AU - Avota, Elita AU - Schneider-Schaulies, Sibylle AU - Meintjes, Ayton AU - Mulder, Nicola AU - Kneitz, Susanne AB - BACKGROUND: Measles virus (MV) causes T cell suppression by interference with phosphatidylinositol-3-kinase (PI3K) activation. We previously found that this interference affected the activity of splice regulatory proteins and a T cell inhibitory protein isoform was produced from an alternatively spliced pre-mRNA. Hypothesis Differentially regulated and alternatively splice variant transcripts accumulating in response to PI3K abrogation in T cells potentially encode proteins involved in T cell silencing. METHODS: To test this hypothesis at the cellular level, we performed a Human Exon 1.0 ST Array on RNAs isolated from T cells stimulated only or stimulated after PI3K inhibition. We developed a simple algorithm based on a splicing index to detect genes that undergo alternative splicing (AS) or are differentially regulated (RG) upon T cell suppression. RESULTS: Applying our algorithm to the data, 9% of the genes were assigned as AS, while only 3% were attributed to RG. Though there are overlaps, AS and RG genes differed with regard to functional regulation, and were found to be enriched in different functional groups. AS genes targeted extracellular matrix (ECM)-receptor interaction and focal adhesion pathways, while RG genes were mainly enriched in cytokine-receptor interaction and Jak-STAT. When combined, AS/RG dependent alterations targeted pathways essential for T cell receptor signaling, cytoskeletal dynamics and cell cycle entry. CONCLUSIONS: PI3K abrogation interferes with key T cell activation processes through both differential expression and alternative splicing, which together actively contribute to T cell suppression. DA - 2013 DB - OpenUCT DO - 10.1371/journal.pone.0050695 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - Accumulation of splice variants and transcripts in response to PI3K inhibition in T cells TI - Accumulation of splice variants and transcripts in response to PI3K inhibition in T cells UR - http://hdl.handle.net/11427/16024 ER - en_ZA


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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 credited. Except where otherwise noted, this item's license is described as 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 credited.