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

Abstract

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 Aβ1 isoform and exon 13 skipped Aβ2 isoform of the catalytic A-subunit of calcineurin phosphatase. These findings reveal a crucial role for PTBP1 in regulating CD8 T cell activation.

An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells

“…For Oxford Nanopore Technologies (ONT) sequencing, libraries were prepared as described previously 88, 89 . Briefly, RNA was reverse transcribed using the Smart-seq2 protocol 90 , cDNA was amplified using the KAPA HiFi Uracil+ hot start polymerase mix (Roche) and PCR products were purified using 0.6X AMPure XP beads (Beckman).…”