Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/216832
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Detection of a G-Quadruplex as a Regulatory Element in Thymidylate synthase for Gene Silencing Using Polypurine Reverse Hoogsteen Hairpins |
Autor: | Aubets, Eva; Félix, Alex J.; Garavís, Miguel CSIC ORCID; Reyes, Laura; Aviñó, Anna CSIC ORCID; Eritja Casadellà, Ramón CSIC ORCID ; Ciudad, Carlos J.; Noé, Véronique | Palabras clave: | G-quadruplex PPRH Thymidylate synthase Anti-tumor therapy 5-fluorouracil Gene silencing Gene regulation |
Fecha de publicación: | 25-jun-2020 | Editor: | Multidisciplinary Digital Publishing Institute | Citación: | International Journal of Molecular Sciences 21 (14): 5028 (2020) | Resumen: | Thymidylate synthase (TYMS) enzyme is an anti-cancer target given its role in DNA biosynthesis. TYMS inhibitors (e.g., 5-Fluorouracil) can lead to drug resistance through an autoregulatory mechanism of TYMS that causes its overexpression. Since G-quadruplexes (G4) can modulate gene expression, we searched for putative G4 forming sequences (G4FS) in the TYMS gene that could be targeted using polypurine reverse Hoogsteen hairpins (PPRH). G4 structures in the TYMS gene were detected using the quadruplex forming G-rich sequences mapper and confirmed through spectroscopic approaches such as circular dichroism and NMR using synthetic oligonucleotides. Interactions between G4FS and TYMS protein or G4FS and a PPRH targeting this sequence (HpTYMS-G4-T) were studied by EMSA and thioflavin T staining. We identified a G4FS in the 5’UTR of the TYMS gene in both DNA and RNA capable of interacting with TYMS protein. The PPRH binds to its corresponding target dsDNA, promoting G4 formation. In cancer cells, HpTYMG-G4-T decreased TYMS mRNA and protein levels, leading to cell death, and showed a synergic effect when combined with 5-fluorouracil. These results reveal the presence of a G4 motif in the TYMS gene, probably involved in the autoregulation of TYMS expression, and the therapeutic potential of a PPRH targeted to the G4FS. | Versión del editor: | https://doi.org/10.3390/ijms21145028 | URI: | http://hdl.handle.net/10261/216832 | DOI: | 10.3390/ijms21145028 |
Aparece en las colecciones: | (IQAC) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
Auberts2020IJMS_ThySyn.pdf | Artículo principal | 3,33 MB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
3
checked on 15-abr-2024
SCOPUSTM
Citations
6
checked on 15-abr-2024
WEB OF SCIENCETM
Citations
6
checked on 24-feb-2024
Page view(s)
146
checked on 23-abr-2024
Download(s)
213
checked on 23-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
Artículos relacionados:
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.