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UPF1 silenced cellular model systems for screening of read-through agents active on β039 thalassemia point mutation.
- Source :
- BMC Biotechnology; 5/15/2018, Vol. 18 Issue 1, pN.PAG-N.PAG, 1p
- Publication Year :
- 2018
-
Abstract
- Background: Nonsense mutations promote premature translational termination, introducing stop codons within the coding region of mRNAs and causing inherited diseases, including thalassemia. For instance, in β<superscript>0</superscript>39 thalassemia the CAG (glutamine) codon is mutated to the UAG stop codon, leading to premature translation termination and to mRNA destabilization through the well described NMD (nonsense-mediated mRNA decay). In order to develop an approach facilitating translation and, therefore, protection from NMD, ribosomal read-through molecules, such as aminoglycoside antibiotics, have been tested on mRNAs carrying premature stop codons. These findings have introduced new hopes for the development of a pharmacological approach to the β<superscript>0</superscript>39 thalassemia therapy. While several strategies, designed to enhance translational read-through, have been reported to inhibit NMD efficiency concomitantly, experimental tools for systematic analysis of mammalian NMD inhibition by translational read-through are lacking. Results: We developed a human cellular model of the β<superscript>0</superscript>39 thalassemia mutation with UPF-1 suppressed and showing a partial NMD suppression. Conclusions: This novel cellular model could be used for the screening of molecules exhibiting preferential read-through activity allowing a great rescue of the mutated transcripts. [ABSTRACT FROM AUTHOR]
- Subjects :
- THALASSEMIA treatment
NONSENSE mutation
MESSENGER RNA
STOP codons
PHARMACOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 14726750
- Volume :
- 18
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- BMC Biotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 129619446
- Full Text :
- https://doi.org/10.1186/s12896-018-0435-0