Journal
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
Volume 94, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.etap.2022.103921
Keywords
Alternativesplicing; Arsenic; Zincsupplementation; ZRANB2; TRA2B
Funding
- National Institutes of Health, USA [R25CA134283, R01ES027778, R21ES030334, P30ES030283]
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Inorganic arsenic exposure can displace zinc from zinc fingers of the splice regulator ZRANB2, disrupting its role in the splicing of its target TRA2B. However, zinc supplementation can prevent the disruption of ZRANB2 splice function caused by iAs, suggesting a potential preventive measure against iAs-mediated diseases.
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 pre-vented 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.
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