PKC-theta is a novel SC35 splicing factor regulator in response to T cell activation

Robert MCCUAIG, Jenny DUNN, Jasmine Li, Antonia Masch, Tobias Knaute, Mike Schutkowski, Johannes Zerweck, Sudha RAO

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Alternative splicing of nuclear pre-mRNA is essential for generating protein diversity and regulating gene expression. While many immunologically relevant genes undergo alternative splicing, the role of regulated splicing in T cell immune responses is largely unexplored, and the signaling pathways and splicing factors that regulate alternative splicing in T cells are poorly defined. Here, we show using a combination of Jurkat T cells, human primary T cells, and ex vivo naïve and effector virus-specific T cells isolated after influenza A virus infection that SC35 phosphorylation is induced in response to stimulatory signals. We show that SC35 colocalizes with RNA polymerase II in activated T cells and spatially overlaps with H3K27ac and H3K4me3, which mark transcriptionally active genes. Interestingly, SC35 remains coupled to the active histone marks in the absence of continuing stimulatory signals. We show for the first time that nuclear PKC-¿ co-exists with SC35 in the context of the chromatin template and is a key regulator of SC35 in T cells, directly phosphorylating SC35 peptide residues at RNA recognition motif and RS domains. Collectively, our findings suggest that nuclear PKC-¿ is a novel regulator of the key splicing factor SC35 in T cells.
Original languageEnglish
Pages (from-to)1-14
Number of pages14
JournalFrontiers in Immunology
Volume6
Issue numberNOV
DOIs
Publication statusPublished - 2015

Fingerprint

T-Lymphocytes
Alternative Splicing
Histone Code
Jurkat Cells
RNA Splicing Factors
RNA Polymerase II
RNA Precursors
Influenza A virus
Virus Diseases
Genes
Chromatin
Phosphorylation
Viruses
Gene Expression
Peptides
Proteins

Cite this

MCCUAIG, Robert ; DUNN, Jenny ; Li, Jasmine ; Masch, Antonia ; Knaute, Tobias ; Schutkowski, Mike ; Zerweck, Johannes ; RAO, Sudha. / PKC-theta is a novel SC35 splicing factor regulator in response to T cell activation. In: Frontiers in Immunology. 2015 ; Vol. 6, No. NOV. pp. 1-14.
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abstract = "Alternative splicing of nuclear pre-mRNA is essential for generating protein diversity and regulating gene expression. While many immunologically relevant genes undergo alternative splicing, the role of regulated splicing in T cell immune responses is largely unexplored, and the signaling pathways and splicing factors that regulate alternative splicing in T cells are poorly defined. Here, we show using a combination of Jurkat T cells, human primary T cells, and ex vivo na{\"i}ve and effector virus-specific T cells isolated after influenza A virus infection that SC35 phosphorylation is induced in response to stimulatory signals. We show that SC35 colocalizes with RNA polymerase II in activated T cells and spatially overlaps with H3K27ac and H3K4me3, which mark transcriptionally active genes. Interestingly, SC35 remains coupled to the active histone marks in the absence of continuing stimulatory signals. We show for the first time that nuclear PKC-¿ co-exists with SC35 in the context of the chromatin template and is a key regulator of SC35 in T cells, directly phosphorylating SC35 peptide residues at RNA recognition motif and RS domains. Collectively, our findings suggest that nuclear PKC-¿ is a novel regulator of the key splicing factor SC35 in T cells.",
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PKC-theta is a novel SC35 splicing factor regulator in response to T cell activation. / MCCUAIG, Robert; DUNN, Jenny; Li, Jasmine; Masch, Antonia; Knaute, Tobias; Schutkowski, Mike; Zerweck, Johannes; RAO, Sudha.

In: Frontiers in Immunology, Vol. 6, No. NOV, 2015, p. 1-14.

Research output: Contribution to journalArticle

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AU - MCCUAIG, Robert

AU - DUNN, Jenny

AU - Li, Jasmine

AU - Masch, Antonia

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AU - Schutkowski, Mike

AU - Zerweck, Johannes

AU - RAO, Sudha

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AB - Alternative splicing of nuclear pre-mRNA is essential for generating protein diversity and regulating gene expression. While many immunologically relevant genes undergo alternative splicing, the role of regulated splicing in T cell immune responses is largely unexplored, and the signaling pathways and splicing factors that regulate alternative splicing in T cells are poorly defined. Here, we show using a combination of Jurkat T cells, human primary T cells, and ex vivo naïve and effector virus-specific T cells isolated after influenza A virus infection that SC35 phosphorylation is induced in response to stimulatory signals. We show that SC35 colocalizes with RNA polymerase II in activated T cells and spatially overlaps with H3K27ac and H3K4me3, which mark transcriptionally active genes. Interestingly, SC35 remains coupled to the active histone marks in the absence of continuing stimulatory signals. We show for the first time that nuclear PKC-¿ co-exists with SC35 in the context of the chromatin template and is a key regulator of SC35 in T cells, directly phosphorylating SC35 peptide residues at RNA recognition motif and RS domains. Collectively, our findings suggest that nuclear PKC-¿ is a novel regulator of the key splicing factor SC35 in T cells.

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