Immediate early splicing controls de novo protein synthesis after T cell activation

Immediate early genes have been known and studied for decades. Their fast and transient induction, which depends on phosphorylation cascades and is independent of de novo protein synthesis, orchestrates the cellular response to various stimuli. In this study we show that the same phosphorylation cascades also target the splicing machinery to induce an analogous splicing switch that we call immediate early splicing (IES). We characterize hnRNPC2-controlled IES, which depends on the MEK-ERK pathway and the T cell specific PKC?. This splicing switch mainly targets components of the translation machinery and contributes to reduced de novo protein synthesis early upon T cell activation, to coordinate extensive transcriptional and posttranscriptional changes in gene expression. Together, our data set a paradigm for fast and transient alternative splicing, the immediate cellular response to activation, and provide evidence for its functional relevance during T cell activation. Overall design: Jurkat T cells were stimulated with PMA for 0, 30 and 120 minutes. Nascent RNA was analyzed by RNA-seq. Additionally, Hek or HeLa cells treated with a morpholino to change the hnRNPC1/C2 ratio and polyA+ RNA was investigated by RNA-seq.