Polypyrimidine Tract Binding Protein 1 regulates the activation of mouse CD8 T cells

We show that the RNA-binding protein Polypyrimidine Tract Binding Protein 1 (PTBP1) is dispensable for the development of naïve mouse CD8 T cells, but is necessary for the optimal expansion and production of effector molecules by antigen-specific CD8 T cells in vivo. PTBP1 has an essential role in regulating the early events following activation of the naïve CD8 T cell leading to IL-2 and TNF production. It is also required to protect activated CD8 T cells from apoptosis. PTBP1 controls alternative splicing of over 400 genes in naïve CD8 T cells in addition to regulating the abundance of ~200 mRNAs. PTBP1 is required for the nuclear accumulation of c-Fos, NFATc2 and NFATc3, but not NFATc1. This selective effect on NFAT proteins correlates with PTBP1-promoted expression of the shorter Ab1 isoform and exon 13 skipped Ab2 isoform of the catalytic A-sububit of calcineurin phosphatse. These findings reveal a crucial role for PTBP1 in regulating CD8 T cell activation. Short-read Illumina mRNA-seq libraries were generated from naïve and activated CD8 T cells from control and PTBP1 conditional knockout mice, with four biological replicates per condition. The corresponding replicates for naïve and activated samples for a given genotype were from the same mouse. Long-read ONT cDNA-PCR libraries were also generated from the same RNA samples as the Illumina libraries, except that the fourth replicate for activated cells was omitted. PTBP1 iCLIP libraries were prepared from activated CD8 T cells, with four biological replicates in control cells, and two biological replicates in PTBP1 conditional knockout cells as a negative control.