RNPS1 in PSAP complex controls periodic pre-mRNA splicing over the cell cycle
Kazuhiro Fukumura,
Akio Masuda,
Jun-ichi Takeda,
Osamu Nagano,
Hideyuki Saya,
Kinji Ohno,
Akila Mayeda
Affiliations
Kazuhiro Fukumura
Division of Gene Regulation, Oncology Innovation Center, Fujita Health University, Toyoake, Aichi 470-1192, Japan; Corresponding author
Akio Masuda
Division of Neurogenetics, Center for Neurological Disease and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan
Jun-ichi Takeda
Division of Neurogenetics, Center for Neurological Disease and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan
Osamu Nagano
Division of Gene Regulation, Oncology Innovation Center, Fujita Health University, Toyoake, Aichi 470-1192, Japan
Hideyuki Saya
Division of Gene Regulation, Oncology Innovation Center, Fujita Health University, Toyoake, Aichi 470-1192, Japan
Kinji Ohno
Division of Neurogenetics, Center for Neurological Disease and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan; Graduate School of Nutritional Sciences, Nagoya University of Arts and Sciences, Nisshin, Aichi 470-0196, Japan
Akila Mayeda
Division of Gene Regulation, Oncology Innovation Center, Fujita Health University, Toyoake, Aichi 470-1192, Japan; xFOREST Therapeutics Co., Ltd., Kajii-cho, Kamigyo-ku, Kyoto 602-0841, Japan; Corresponding author
Summary: Cell cycle progression requires periodic gene expression through splicing control. However, the splicing factor that directly controls this cell cycle-dependent splicing remains 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.
