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

Simple item page
dc.contributor.authorRiedel, Aliceen_ZA
dc.contributor.authorMofolo, Boitumeloen_ZA
dc.contributor.authorAvota, Elitaen_ZA
dc.contributor.authorSchneider-Schaulies, Sibylleen_ZA
dc.contributor.authorMeintjes, Aytonen_ZA
dc.contributor.authorMulder, Nicolaen_ZA
dc.contributor.authorKneitz, Susanneen_ZA
dc.date.accessioned2015-12-28T06:47:22Z
dc.date.available2015-12-28T06:47:22Z
dc.date.issued2013en_ZA
dc.description.abstractBACKGROUND: 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.identifier.apacitationRiedel, 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/11427/16024en_ZA
dc.identifier.chicagocitationRiedel, 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/11427/16024en_ZA
dc.identifier.citationRiedel, 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.0050695en_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
dc.identifier.urihttp://hdl.handle.net/11427/16024
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0050695
dc.identifier.vancouvercitationRiedel 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.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis 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.holder© 2013 Riedel et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherGene regulationen_ZA
dc.subject.otherAlternative splicingen_ZA
dc.subject.otherMeasles virusen_ZA
dc.subject.otherT cell receptorsen_ZA
dc.subject.otherReverse transcriptase-polymerase chain reactionen_ZA
dc.subject.otherTCR signaling cascadeen_ZA
dc.subject.otherCell cycle and cell divisionen_ZA
dc.titleAccumulation of splice variants and transcripts in response to PI3K inhibition in T cellsen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Riedel_Accumulation_of_Splice_Variants_2013.pdf
Size:
634.71 KB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Journal Articles