RNPS1 in PSAP complex controls periodic pre-mRNA splicing over the cell cycle

Cell cycle progression requires periodic gene expression through splicing control. However, the splicing factor that directly controls this cell cycle-dependent splicing remain unknown. Cell cycle-dependent expression of the AURKB (aurora kinase B) gene is essential for chromosome segregation and cytokinesis. We previously reported that RNPS1 is essential to maintain precise splicing in AURKB intron 5. Here we show that RNPS1 plays this role in PSAP complex with PNN and SAP18, but not ASAP complex with ACIN1 and SAP18. Whole-transcriptome sequencing of RNPS1- and PNN-deficient cells indicated that RNPS1, either alone or as PSAP complex, is an essential splicing factor for a subset of introns. Remarkably, protein expression of RNPS1, but not PNN, is coordinated with cyclical splicing in PSAP-controlled introns including AURKB intron 5. The ubiquitin-proteasome pathway is involved in the periodic decrease of RNPS1 protein level. RNPS1 is a key factor that controls periodic splicing during the cell cycle. O_FIG O_LINKSMALLFIG WIDTH=185 HEIGHT=200 SRC="FIGDIR/small/567984v3_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@84475dorg.highwire.dtl.DTLVardef@693637org.highwire.dtl.DTLVardef@16678feorg.highwire.dtl.DTLVardef@917ee0_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThe AURKB gene encodes a protein kinase essential for cytokinesis and cell cycle C_LIO_LIPSAP complex (RNPS1, PNN, SAP18) is required for precise splicing in AURKB intron 5 C_LIO_LIRNPS1 protein in PSAP complex controls periodical splicing during the cell cycle C_LIO_LICyclical decrease of RNPS1 protein is mediated by the ubiquitin-proteasome pathway C_LI