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Título

New insights into the RNA-based mechanism of action of the anticancer drug 5'-Fluorouracil in eukaryotic cells

AutorMojardín, Laura CSIC; Botet, Javier CSIC; Quintales, Luis CSIC ORCID; Moreno, Sergio CSIC ORCID; Salas, Margarita CSIC ORCID
Fecha de publicación2013
EditorPublic Library of Science
CitaciónPLoS ONE 8(11): e78171 (2013)
Resumen5-Fluorouracil (5FU) is a chemotherapeutic drug widely used in treating a range of advanced, solid tumours and, in particular, colorectal cancer. Here, we used high-density tiling DNA microarray technology to obtain the specific transcriptome-wide response induced by 5FU in the eukaryotic model Schizosaccharomyces pombe. This approach combined with real-time quantitative PCR analysis allowed us to detect splicing defects of a significant number of intron-containing mRNA, in addition to identify some rRNA and tRNA processing defects after 5FU treatment. Interestingly, our studies also revealed that 5FU specifically induced the expression of certain genes implicated in the processing of mRNA, tRNA and rRNA precursors, and in the post-transcriptional modification of uracil residues in RNA. The transcription of several tRNA genes was also significantly induced after drug exposure. These transcriptional changes might represent a cellular response mechanism to counteract 5FU damage since deletion strains for some of these up-regulated genes were hypersensitive to 5FU. Moreover, most of these RNA processing genes have human orthologs that participate in conserved pathways, suggesting that they could be novel targets to improve the efficacy of 5FU-based treatments.
DescripciónThis is an open-access article distributed under the terms of the Creative Commons Attribution License.
Versión del editorhttp://dx.doi.org/10.1371/journal.pone.0078172
URIhttp://hdl.handle.net/10261/116153
DOI10.1371/journal.pone.0078172
Identificadoresdoi: 10.1371/journal.pone.0078172
issn: 1932-6203
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