An internal promoter drives the expression of a truncated form of ccc1 capable of protecting yeast from iron toxicity

Funding Information: This work was supported by Project LISBOA-01-0145-FEDER-007660 (?Microbiologia Molecular, Estrutural e Celular?) funded by FEDER funds through COMPETE2020??Programa Operacional Competitividade e Internacionaliza??o? (POCI); ?Funda??o para a Ci?ncia e a Tecnologia? (FCT) grants EXPL/BIA-MIC/2525/2013 and programme IF (IF/00124/2015) to C.P.; grant PTDC/BIA-BQM/31317/2017 to C.V.R.; the European Union?s Horizon 2020 research and innovation programme under grant agreement No. 810856 and 857203; COST Action CA15133, supported by COST (European Cooperation in Science and Technology) and PPBI?Portuguese Platform of BioImaging (PPBI-POCI-01-0145-FEDER-022122) co-funded by national funds from OE??Or?amento de Estado? and by FEDER. C.A. (SFRH/BPD/74294/2010), S.M.C. (SFRH/BD/91077/2012), C.V.R. (SFRH/BPD/94050/2013) and A.G.-C. (SFRH/BD/118866/2016) were supported by FCT contracts or fellowships. Funding Information: Funding: This work was supported by Project LISBOA-01-0145-FEDER-007660 (“Microbiologia Molecular, ?strutural e Celular”) funded by F?D?R funds through COMP?T?2020—“Programa Operacional Competitividade e Internacionalização” (POCI); “Fundação para a Ciência e a Tecno-logia” (FCT) grants ?XPL/BIA-MIC/2525/2013 and programme IF (IF/00124/2015) to C.P.; grant PTDC/BIA-BQM/31317/2017 to C.V.R.; the ?uropean Union’s Horizon 2020 research and innovation programme under grant agreement No. 810856 and 857203; COST Action CA15133, supported by COST (European Cooperation in Science and Technology) and PPBI—Portuguese Platform of Bi-oImaging (PPBI-POCI-01-0145-FEDER-022122) co-funded by national funds from OE—“Orçamento de Estado” and by FEDER. C.A. (SFRH/BPD/74294/2010), S.M.C. (SFRH/BD/91077/2012), C.V.R. (SFRH/BPD/94050/2013) and A.G.-C. (SFRH/BD/118866/2016) were supported by FCT contracts or fellowships. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.In yeast, iron storage and detoxification depend on the Ccc1 transporter that mediates iron accumulation in vacuoles. While deletion of the CCC1 gene renders cells unable to survive under iron overload conditions, the deletion of its previously identified regulators only partially affects survival, indicating that the mechanisms controlling iron storage and detoxification in yeast are still far from well understood. This work reveals that CCC1 is equipped with a complex transcriptional structure comprising several regulatory regions. One of these is located inside the coding sequence of the gene and drives the expression of a short transcript encoding an N-terminally truncated protein, designated as s-Ccc1. s-Ccc1, though less efficiently than Ccc1, is able to promote metal accumulation in the vacuole, protecting cells against iron toxicity. While the expression of the s-Ccc1 appears to be repressed in the normal genomic context, our current data clearly demonstrates that it is functional and has the capacity to play a role under iron overload conditions.publishersversionpublishe