RNPS1 in PSAP complex controls Pre-mRNA splicing with periodicity during cell cycle

The cell cycle progression requires periodic expression of the associated genes through the control of splicing. However, the factor that directly controls the cell cycle-dependent splicing has remained unknown. The cell cycle-dependent expression of AURKB (aurora kinase B) gene is essential in chromosome segregation and cytokinesis. We previously reported that RNPS1 depletion induces multiple aberrant splicing in AURKB intron 5, causing a reduction of the AURKB protein and the eventual abnormal multinucleation. We show that RNPS1 functions in PSAP complex (PNN, SAP18 and RNPS1) but not ASAP (ASIN1, SAP18 and RNPS1). Our transcriptome-wide analysis of RNPS1- and PNN-deficient cells indicates that PSAP globally controls pre-mRNA splicing involved in cell cycle progression. Remarkably, protein expression of RNPS1, but not PNN, is cell cycle-dependently coordinated with splicing in PSAP-controlled introns, including AURKB intron 5, implicating that RNPS1 is a key factor in controlling the periodic splicing during cell cycle.