当前位置: X-MOL 学术RNA Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Deoxynivalenol globally affects the selection of 3' splice sites in human cells by suppressing the splicing factors, U2AF1 and SF1.
RNA Biology ( IF 4.1 ) Pub Date : 2020-02-06 , DOI: 10.1080/15476286.2020.1719750
Zhangsheng Hu 1, 2 , Yu Sun 1, 2 , Jiongjie Chen 1, 2 , Yurong Zhao 1, 2 , Han Qiao 1, 2 , Ruohong Chen 1, 2 , Xianhui Wen 1, 2 , Yiqun Deng 1, 2 , Jikai Wen 1, 2
Affiliation  

Deoxynivalenol (DON) is one of the most abundant mycotoxins and has adverse effects on several biological processes, posing risks of protein synthesis-disrupting effects and ribotoxic response. Therefore, chronic exposure to DON would fundamentally reshape the global expression pattern. Whether DON causes toxic effects on mRNA splicing, a fundamental biological process, remains unclear. In this study, we found that administration of the relative low dosage of DON dramatically changed the alternative splicing of pre-mRNA in HepG2 cells. The overall number of transcripts with aberrant selection of 3' splice sites was significantly increased in DON-exposed HepG2 cells. This effect was further confirmed in two other human cell lines, HEK293 and Caco-2, suggesting that this DON-induced alteration in splicing patterns was universal in human cells. Among these DON-induced changes in alternative splicing, the expression levels of two related splicing factors, SF1 and U2AF1, which are essential for 3' splice site recognitions, were strongly suppressed. Overexpression of either of the two splicing factors strongly alleviated the DON-induced aberrant selection of 3' splice sites. Moreover, SF1 was required for human cell proliferation in DON exposure, and the restoration of SF1 expression partially reinstated the proliferation potential for DON-treated cells. In conclusion, our study suggests that DON, even at a low dosage, has great potential to change gene expression globally by affecting not only protein synthesis but also mRNA processing in human cells.

中文翻译:

脱氧雪腐烯醇通过抑制剪接因子U2AF1和SF1全局影响人细胞中3'剪接位点的选择。

脱氧雪腐烯醇(DON)是最丰富的霉菌毒素之一,对几种生物学过程均具有不利影响,存在破坏蛋白质合成和核毒性反应的风险。因此,长期暴露于DON将从根本上改变全球表达方式。DON是否对mRNA剪接(一种基本的生物学过程)产生毒性影响,目前尚不清楚。在这项研究中,我们发现相对较低剂量的DON的施用显着改变了HepG2细胞中pre-mRNA的选择性剪接。在DON暴露的HepG2细胞中,异常选择3'剪接位点的转录物总数显着增加。这种效应在另外两个人类细胞系HEK293和Caco-2中得到了进一步证实,表明这种DON诱导的剪接模式改变在人类细胞中是普遍的。在这些DON诱导的选择性剪接变化中,强烈抑制了两个相关剪接因子SF1和U2AF1的表达水平,这对于3'剪接位点的识别至关重要。两个剪接因子中任一个的过表达都大大减轻了DON诱导的3'剪接位点的异常选择。此外,在DON暴露下人细胞增殖需要SF1,而SF1表达的恢复部分恢复了DON处理的细胞的增殖潜力。总之,我们的研究表明,即使是低剂量的DON,也不仅通过影响人类细胞中的蛋白质合成而且还影响mRNA的加工,具有改变全球基因表达的巨大潜力。对3'剪接位点识别必不可少的蛋白被强烈抑制。两个剪接因子中任一个的过表达都大大减轻了DON诱导的3'剪接位点的异常选择。此外,在DON暴露下人细胞增殖需要SF1,而SF1表达的恢复部分恢复了DON处理的细胞的增殖潜力。总之,我们的研究表明,即使是低剂量的DON,也不仅通过影响人类细胞中的蛋白质合成而且还影响mRNA的加工,具有改变全球基因表达的巨大潜力。对3'剪接位点识别必不可少的蛋白被强烈抑制。两个剪接因子中任一个的过表达都大大减轻了DON诱导的3'剪接位点的异常选择。此外,在DON暴露下人细胞增殖需要SF1,而SF1表达的恢复部分恢复了DON处理的细胞的增殖潜力。总而言之,我们的研究表明,即使是低剂量的DON,也不仅通过影响人类细胞中蛋白质的合成而且还影响mRNA的加工,具有改变全球基因表达的巨大潜力。SF1是DON暴露下人细胞增殖所必需的,SF1表达的恢复部分恢复了DON处理过的细胞的增殖潜力。总之,我们的研究表明,即使是低剂量的DON,也不仅通过影响人类细胞中的蛋白质合成而且还影响mRNA的加工,具有改变全球基因表达的巨大潜力。SF1是DON暴露下人细胞增殖所必需的,SF1表达的恢复部分恢复了DON处理过的细胞的增殖潜力。总之,我们的研究表明,即使是低剂量的DON,也不仅通过影响人类细胞中的蛋白质合成而且还影响mRNA的加工,具有改变全球基因表达的巨大潜力。
更新日期:2020-03-22
down
wechat
bug