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Global analysis of alternative splicing during T-cell activation

¹ Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5S 3EI, Canada
² Department of Molecular and Medical Genetics and Centre for Cellular and Bimolecular Research, University of Toronto, Toronto, Ontario M5S 3EI, Canada
³ Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA

The role of alternative splicing (AS) in eliciting immune responses is poorly understood. We used quantitative AS microarray profiling to survey changes in AS during activation of Jurkat cells, a leukemia-derived T-cell line. Our results indicate that 10%–15% of the profiled alternative exons undergo a >10% change in inclusion level during activation. The majority of the genes displaying differential AS levels are distinct from the set of genes displaying differential transcript levels. These two gene sets also have overlapping yet distinct functional roles. For example, genes that show differential AS patterns during T-cell activation are often closely associated with cell-cycle regulation, whereas genes with differential transcript levels are highly enriched in functions associated more directly with immune defense and cytoskeletal architecture. Previously unknown AS events were detected in genes that have important roles in T-cell activation, and these AS level changes were also observed during the activation of normal human peripheral CD4+ and CD8+ lymphocytes. In summary, by using AS microarray profiling, we have discovered many new AS changes associated with T-cell activation. Our results suggest an extensive role for AS in the regulation of the mammalian immune response.

Keywords: alternative splicing; T-cell activation; T lymphocytes; microarray

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