Fukumura Kazuhiro, Masuda Akio, Takeda Jun-Ichi, Nagano Osamu, Saya Hideyuki, Ohno Kinji, Mayeda Akila
Division of Gene Regulation, Oncology Innovation Center, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
Division of Neurogenetics, Center for Neurological Disease and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
iScience. 2024 Nov 15;27(12):111400. doi: 10.1016/j.isci.2024.111400. eCollection 2024 Dec 20.
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 (aurora kinase B) gene is essential for chromosome segregation and cytokinesis. We previously reported that RNPS1 is essential to maintain precise splicing in 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 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.
细胞周期进程需要通过剪接控制来实现周期性基因表达。然而，直接控制这种细胞周期依赖性剪接的剪接因子仍不清楚。极光激酶B基因的细胞周期依赖性表达对于染色体分离和胞质分裂至关重要。我们之前报道过，RNPS1对于维持极光激酶B基因第5内含子的精确剪接至关重要。在此我们表明，RNPS1在与PNN和SAP18组成的PSAP复合物中发挥这一作用，而不是在与ACIN1和SAP18组成的ASAP复合物中。对缺乏RNPS1和PNN的细胞进行的全转录组测序表明，RNPS1单独或作为PSAP复合物，是一部分内含子的必需剪接因子。值得注意的是，RNPS1而非PNN的蛋白表达与包括极光激酶B基因第5内含子在内的PSAP控制的内含子中的周期性剪接相协调。泛素-蛋白酶体途径参与了RNPS1蛋白水平的周期性降低。RNPS1是控制细胞周期中周期性剪接的关键因子。
