Kano Shizuka, Nishida Kensei, Nishiyama Chihiro, Akaike Yoko, Kajita Keisuke, Kurokawa Ken, Masuda Kiyoshi, Kuwano Yuki, Tanahashi Toshihito, Rokutan Kazuhito
Department of Stress Science, Institute of Health Biosciences, the University of Tokushima Graduate School.
J Med Invest. 2013;60(3-4):228-35. doi: 10.2152/jmi.60.228.
Serine/arginine-rich splicing factor 3 (SRSF3), a member of the SRSF family, plays a wide-ranging role in gene expression. The human SRSF3 gene generates a major mRNA isoform encoding a functional, full-length protein and a PTC-containing isoform (SRSF3-PTC). The latter is expected to be degraded through the nonsense-mediated mRNA decay system. However, it was reported that SRSF3-PTC mRNA was produced under stressful conditions and translated into a truncated SRSF3 protein (SRSF3-TR). To disclose unknown functions of SRSF3-TR, we established Flp-In-293 cells stably expressing SRSF3-TR. The SRSF3-TR-expressing cells increased mRNA and protein levels of positive regulators for G1 to S phase transition (cyclin D1, cyclin D3, CDC25A, and E2F1) and accelerated their growth. c-Jun is required for progression through the G1 phase, the mechanism by which involves transcriptional control of the cyclin D1 gene. We also found that the JUN promoter activity was significantly increased in the Flp-In-293 cells stably expressing SRSF3-TR, compared with mock-transfected control cells. The SRSF3-TR-expressing cells increased c-Jun and Sp-1 levels, which are important for the positive autoregulation and basal transcription of JUN, respectively. Our results suggest that stress-inducible SRSF3-TR may participate in the acceleration of cell growth through facilitating c-Jun-mediated G1 progression under stressful conditions.
富含丝氨酸/精氨酸的剪接因子3（SRSF3）是SRSF家族的成员之一，在基因表达中发挥着广泛作用。人类SRSF3基因产生一种主要的mRNA异构体，编码一种功能性的全长蛋白以及一种含提前终止密码子的异构体（SRSF3-PTC）。后者预计会通过无义介导的mRNA降解系统被降解。然而，有报道称SRSF3-PTC mRNA在应激条件下产生，并被翻译成截短的SRSF3蛋白（SRSF3-TR）。为了揭示SRSF3-TR的未知功能，我们构建了稳定表达SRSF3-TR的Flp-In-293细胞。表达SRSF3-TR的细胞增加了G1期到S期转换的正向调节因子（细胞周期蛋白D1、细胞周期蛋白D3、细胞周期蛋白依赖性激酶25A和E2F1）的mRNA和蛋白水平，并加速了它们的生长。c-Jun是G1期进程所必需的，其机制涉及细胞周期蛋白D1基因的转录调控。我们还发现，与mock转染的对照细胞相比，稳定表达SRSF3-TR的Flp-In-293细胞中JUN启动子活性显著增加。表达SRSF3-TR的细胞增加了c-Jun和Sp-1的水平，它们分别对JUN的正向自动调节和基础转录很重要。我们的结果表明，应激诱导的SRSF3-TR可能通过在应激条件下促进c-Jun介导的G1期进程来参与细胞生长的加速。
