E2F1 is a transcription factor classically known to regulate G₀/G₁ to S phase progression in the cell cycle. In addition, E2F1 also regulates a wide range of apoptotic genes and thus has been well studied in the context of neuronal death and neurodegenerative diseases. However, its function and regulation in the mature central nervous system are not well understood. Alternative splicing is a well-conserved post-transcriptional mechanism common in cells of the CNS and is necessary to generate diverse functional modifications to RNA or protein products from genes. Heretofore, physiologically significant alternatively spliced E2F1 transcripts have not been reported. In the present study, we report the identification of two novel alternatively spliced E2F1 transcripts: E2F1b, an E2F1 transcript retaining intron 5, and E2F1c, an E2F1 transcript excluding exon 6. These alternatively spliced transcripts are observed in the brain and neural cell types including neurons, astrocytes, and undifferentiated oligodendrocytes. The expression of these E2F1 transcripts is distinct during maturation of primary hippocampal neuroglial cells. Pharmacologically-induced global translation inhibition with cycloheximide, anisomycin or thapsigargin lead to significantly reduced expression of E2F1a, E2F1b and E2F1c. Conversely, increasing neuronal activity by elevating the concentration of potassium chloride selectively increased the expression of E2F1b. Furthermore, experiments expressing these variants in vitro show the transcripts can be translated to generate a protein product. Taken together, our data suggest that the alternatively spliced E2F1 transcript behave differently than the E2F1a transcript, and our results provide a foundation for future investigation of the function of E2F1 splice variants in the CNS.

E2F1是传统上已知的调节G ₀ / G ₁的转录因子到S期在细胞周期中的进展。另外，E2F1还调节广泛的凋亡基因，因此已经在神经元死亡和神经退行性疾病的背景下进行了充分的研究。但是，其在成熟的中枢神经系统中的功能和调节尚不十分清楚。选择性剪接是CNS细胞中常见的一种高度保守的转录后机制，对于从基因产生RNA或蛋白质产物的各种功能修饰而言是必要的。迄今为止，尚未报道具有生理学意义的选择性剪接的E2F1转录物。在本研究中，我们报告了两个新颖的剪接的E2F1转录本的鉴定：E2F1b，一个保留内含子5的E2F1转录本，和E2F1c，一个不包含外显子6的E2F1转录本。在大脑和神经细胞类型（包括神经元，星形胶质细胞和未分化的少突胶质细胞）中观察到这些选择性剪接的转录本。这些E2F1转录本的表达在原代海马神经胶质细胞成熟过程中是不同的。药理学诱导的环己酰亚胺，茴香霉素或毒胡萝卜素的整体翻译抑制作用导致E2F1a，E2F1b和E2F1c的表达显着降低。相反，通过增加氯化钾的浓度来增加神经元活性有选择地增加了E2F1b的表达。此外，在体外表达这些变体的实验表明，转录本可以被翻译以产生蛋白质产物。综上所述，我们的数据表明，选择性剪接的E2F1成绩单的行为与E2F1a成绩单不同，