Gao Chang, Zhai Jie, Dang Shengyuan, Zheng Shimin
a Laboratory Pathological Physiology, College of Veterinary Medicine , Northeast Agricultural University , Harbin , People's Republic of China.
Avian Pathol. 2018 Dec;47(6):585-594. doi: 10.1080/03079457.2018.1511047. Epub 2018 Sep 20.
Alternative splicing (AS) plays a significant role in regulation of genomic expression at the transcriptional level and is involved in many important biological functions of cells, thus a gene can be spliced into distinct transcript variants then translated to many different kinds of protein. Reticuloendotheliosis virus (REV) is a kind of retrovirus that can infect multiple avian species, leading to runting syndrome, immunosuppression and oncogenesis. In this present study, we analyzed AS in REV-infected chicken embryo fibroblasts (CEFs) which were inoculated with the second generation of REV (group VB) and compared with normal CEFs (group C) by high-throughput RNA sequencing technology. A total of 6,939 genes which were alternatively spliced were detected, among them, skipped exon (SE) was the most common pattern. Moreover, 5,607 AS genes were detected as differentially expressed; compared with group C, group VB has 2,825 genes upregulated significantly and 2,782 genes downregulated significantly. These 5,607 differentially expressed AS genes are involved in many important biological processes. Many of them are involved in apoptosis and tumourigenesis. We also proved, by agarose gel electrophoresis, that AS events predicted by our study are authentic and AS is closely related with apoptosis and tumourigenesis in REV-infected CEFs. Our study provides the best analysis to date of the potential link between AS and CEFs in response to REV infection. Research highlights Transcriptomics analysis of REV-infected CEFs using high-throughput sequencing. Potential link between alternative splicing and CEFs in response to REV infection. Skipped exon is the most common spliced pattern in REV-infected CEFs. Differentially expressed genes mainly involved in apoptosis and tumourigenesis.
可变剪接(AS)在转录水平调控基因组表达中发挥着重要作用,并参与细胞的许多重要生物学功能,因此一个基因可以被剪接成不同的转录变体,进而翻译为多种不同类型的蛋白质。网状内皮组织增殖症病毒(REV)是一种逆转录病毒,可感染多种禽类,导致生长发育受阻综合征、免疫抑制和肿瘤发生。在本研究中,我们对接种第二代REV的鸡胚成纤维细胞(CEF)(VB组)进行了可变剪接分析,并通过高通量RNA测序技术与正常CEF(C组)进行比较。共检测到6939个发生可变剪接的基因,其中外显子跳跃(SE)是最常见的模式。此外,检测到5607个可变剪接基因差异表达;与C组相比,VB组有2825个基因显著上调,2782个基因显著下调。这5607个差异表达的可变剪接基因参与许多重要的生物学过程。其中许多基因参与细胞凋亡和肿瘤发生。我们还通过琼脂糖凝胶电泳证明,我们研究预测的可变剪接事件是真实的,并且可变剪接与REV感染的CEF中的细胞凋亡和肿瘤发生密切相关。我们的研究为可变剪接与CEF响应REV感染之间的潜在联系提供了迄今为止最好的分析。研究亮点 使用高通量测序对REV感染的CEF进行转录组学分析。可变剪接与CEF响应REV感染之间的潜在联系。外显子跳跃是REV感染的CEF中最常见的剪接模式。差异表达基因主要参与细胞凋亡和肿瘤发生。