Department of Biochemistry, Purdue University, West Lafayette, Indiana.
Department of Biological Sciences, Purdue University, West Lafayette, Indiana.
Aging Cell. 2018 Oct;17(5):e12817. doi: 10.1111/acel.12817. Epub 2018 Jul 12.
Changes in splicing patterns are a characteristic of the aging transcriptome; however, it is unclear whether these age-related changes in splicing facilitate the progressive functional decline that defines aging. In Drosophila, visual behavior declines with age and correlates with altered gene expression in photoreceptors, including downregulation of genes encoding splicing factors. Here, we characterized the significance of these age-regulated splicing-associated genes in both splicing and visual function. To do this, we identified differential splicing events in either the entire eye or photoreceptors of young and old flies. Intriguingly, aging photoreceptors show differential splicing of a large number of visual function genes. In addition, as shown previously for aging photoreceptors, aging eyes showed increased accumulation of circular RNAs, which result from noncanonical splicing events. To test whether proper splicing was necessary for visual behavior, we knocked down age-regulated splicing factors in photoreceptors in young flies and examined phototaxis. Notably, many of the age-regulated splicing factors tested were necessary for proper visual behavior. In addition, knockdown of individual splicing factors resulted in changes in both alternative splicing at age-spliced genes and increased accumulation of circular RNAs. Together, these data suggest that cumulative decreases in splicing factor expression could contribute to the differential splicing, circular RNA accumulation, and defective visual behavior observed in aging photoreceptors.
剪接模式的变化是衰老转录组的一个特征；然而，尚不清楚这些与年龄相关的剪接变化是否有助于定义衰老的渐进性功能下降。在果蝇中，视觉行为随年龄增长而下降，与感光细胞中基因表达的改变相关，包括编码剪接因子的基因下调。在这里，我们研究了这些年龄调节的剪接相关基因在剪接和视觉功能中的重要性。为此，我们鉴定了年轻和年老果蝇的整个眼睛或感光器中差异剪接事件。有趣的是，衰老的感光器显示出大量视觉功能基因的差异剪接。此外，正如先前对衰老感光器所示，衰老的眼睛表现出环状 RNA 的积累增加，这是由非典型剪接事件引起的。为了测试适当的剪接是否对视觉行为是必要的，我们在年轻的果蝇中敲低了感光器中与年龄相关的剪接因子，并检查了趋光性。值得注意的是，测试的许多与年龄相关的剪接因子对于适当的视觉行为是必需的。此外，单个剪接因子的敲低导致年龄剪接基因的可变剪接和环状 RNA 积累的增加。总之，这些数据表明，剪接因子表达的累积减少可能导致衰老感光器中观察到的差异剪接、环状 RNA 积累和视觉行为缺陷。
