Examining Pathogenesis in Genome Instability Associated Neurodegenerative Mouse Model [polyA-RNA-seq]

DNA damage can promote altered RNA splicing and decreased gene expression (Gregersen and Svejstrup, 2018; Milek et al., 2017; Munoz et al., 2009; Shkreta and Chabot, 2015), and aberrant splicing is implicated in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Fragile X syndrome and spinal muscular atrophy (SMA) (Conlon et al., 2016; Jia et al., 2012; Loomis et al., 2014; Qiu et al., 2014; Scotti and Swanson, 2016). Therefore, we used RNA-seq data to assess RNA-splicing in double-mutant brain tissue using multivariate analysis of transcriptional splicing (rMATS) (Shen et al., 2014) and a splicing deficiency score algorithm (Bai et al., 2013) to assess intron retention. PolyA-enriched RNA sequencing of the cerebellum and cortex examining splicing deficiencies in ATM APTX null and ATM PARP null brains.DNA损伤可促进RNA剪接改变与基因表达下调（Gregersen与Svejstrup，2018；Milek等，2017；Munoz等，2009；Shkreta与Chabot，2015）；而剪接异常与多种神经退行性疾病密切相关，涵盖肌萎缩侧索硬化（amyotrophic lateral sclerosis, ALS）、脆性X综合征（Fragile X syndrome）及脊髓性肌萎缩症（spinal muscular atrophy, SMA）（Conlon等，2016；Jia等，2012；Loomis等，2014；Qiu等，2014；Scotti与Swanson，2016）。因此，本研究采用RNA测序（RNA-seq）数据，通过转录剪接多元分析工具rMATS（Shen等，2014）与剪接缺陷评分算法（Bai等，2013）评估内含子保留情况，以此分析双突变脑组织中的RNA剪接状态。本研究针对小脑与大脑皮层开展polyA富集RNA测序，以检测ATM APTX纯合敲除及ATM PARP纯合敲除脑组织中的剪接缺陷。