生物
RNA剪接
基因敲除
选择性拼接
细胞生物学
细胞周期
外显子
调节器
细胞生长
基因
遗传学
作者
Elena Martín,Claudia Vivori,Malgorzata Rogalska,Jorge Herrero-Vicente,Juan Valcárcel
出处
期刊:RNA
日期:2021-12-01
卷期号:27 (12): 1557-1576
被引量:2
标识
DOI:10.1261/rna.078935.121
摘要
The regulation of pre-mRNA processing has important consequences for cell division and the control of cancer cell proliferation, but the underlying molecular mechanisms remain poorly understood. We report that three splicing factors, SPF45, SR140, and CHERP, form a tight physical and functionally coherent complex that regulates a variety of alternative splicing events, frequently by repressing short exons flanked by suboptimal 3' splice sites. These comprise alternative exons embedded in genes with important functions in cell-cycle progression, including the G2/M key regulator FOXM1 and the spindle regulator SPDL1. Knockdown of either of the three factors leads to G2/M arrest and to enhanced apoptosis in HeLa cells. Promoting the changes in FOXM1 or SPDL1 splicing induced by SPF45/SR140/CHERP knockdown partially recapitulates the effects on cell growth, arguing that the complex orchestrates a program of alternative splicing necessary for efficient cell proliferation.
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