Abstract：
Environmentally relevant (100 nM) inorganic arsenic (iAs) exposure displaces zinc from zinc fingers of upstream splice regulator ZRANB2 disrupting the splicing of its target TRA2B. Excess zinc displaced iAs from ZRANB2 zinc fingers in cell free system. Thus, the hypothesis that zinc supplementation could prevent iAs-mediated disruption of ZRANB2 splice function in human keratinocytes was tested. The data show that zinc supplementation prevented iAs-induced dysregulation of TRA2B splicing by ZRANB2 as well as the induction of ZRANB2 protein expression. These results provide additional support for the hypothesis that zinc supplementation could prevent iAs-mediated disease in iAs-exposed populations.
摘要：
环境相关（100nM）无机砷（iAs）暴露会从上游剪接调节剂ZRANB2的锌指中置换锌，从而破坏其靶标TRA2B的剪接。在无细胞系统中，过量的锌从ZRANB2锌指中取代了iAs。因此，我们测试了补充锌可以防止iAs介导的人角质形成细胞中ZRANB2剪接功能的破坏的假设。数据显示锌补充防止了iAs诱导的ZRANB2对TRA2B剪接的失调以及ZRANB2蛋白表达的诱导。这些结果为补充锌可以预防iAs暴露人群中iAs介导的疾病的假设提供了额外的支持。
