Identifying Potent Nonsense-Mediated mRNA Decay Inhibitors with a Novel Screening System.
genetic disease
nonsense mutation
nonsense-mediated mRNA decay
small molecules
therapy
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
16 Oct 2023
16 Oct 2023
Historique:
received:
18
09
2023
revised:
05
10
2023
accepted:
09
10
2023
medline:
28
10
2023
pubmed:
28
10
2023
entrez:
28
10
2023
Statut:
epublish
Résumé
Nonsense-mediated mRNA decay (NMD) is a quality control mechanism that degrades mRNAs carrying a premature termination codon. Its inhibition, alone or in combination with other approaches, could be exploited to develop therapies for genetic diseases caused by a nonsense mutation. This, however, requires molecules capable of inhibiting NMD effectively without inducing toxicity. We have built a new screening system and used it to identify and validate two new molecules that can inhibit NMD at least as effectively as cycloheximide, a reference NMD inhibitor molecule. These new NMD inhibitors show no cellular toxicity at tested concentrations and have a working concentration between 6.2 and 12.5 µM. We have further validated this NMD-inhibiting property in a physiopathological model of lung cancer in which the
Identifiants
pubmed: 37893174
pii: biomedicines11102801
doi: 10.3390/biomedicines11102801
pmc: PMC10604367
pii:
doi:
Types de publication
Journal Article
Langues
eng
Références
Orphanet J Rare Dis. 2012 Aug 31;7:58
pubmed: 22938201
Biomedicines. 2022 Jan 10;10(1):
pubmed: 35052820
Cell. 2010 Dec 10;143(6):938-50
pubmed: 21145460
Cell Death Differ. 2015 Nov;22(11):1754-63
pubmed: 25744026
Biochim Biophys Acta. 2013 Jun-Jul;1829(6-7):624-33
pubmed: 23500037
J Cell Biol. 2007 Sep 24;178(7):1145-60
pubmed: 17893241
Cancer Res. 2014 Jun 1;74(11):3104-13
pubmed: 24662918
Nucleic Acids Res. 2021 Nov 8;49(19):11022-11037
pubmed: 34634811
EMBO J. 2001 Apr 2;20(7):1785-96
pubmed: 11285241
Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5171-5
pubmed: 1375758
Mol Cell. 2022 Aug 4;82(15):2779-2796.e10
pubmed: 35675814
PLoS One. 2017 Nov 13;12(11):e0187930
pubmed: 29131862
J Med Genet. 2005 Apr;42(4):350-7
pubmed: 15805162
Biomedicines. 2023 Feb 27;11(3):
pubmed: 36979701
Nat Commun. 2020 Mar 20;11(1):1509
pubmed: 32198346
Nature. 2010 May 13;465(7295):227-30
pubmed: 20463739
Hum Mutat. 2008 Aug;29(8):1037-47
pubmed: 18454449
Org Biomol Chem. 2016 Feb 28;14(8):2487-97
pubmed: 26815337
Nat Commun. 2015 Mar 26;6:6632
pubmed: 25808464
Cell Mol Life Sci. 2021 May;78(10):4677-4701
pubmed: 33751142
Trends Genet. 2021 Feb;37(2):143-159
pubmed: 33008628
Genes Dev. 2006 Feb 1;20(3):355-67
pubmed: 16452507
Curr Opin Genet Dev. 2018 Feb;48:44-50
pubmed: 29121514
EMBO Mol Med. 2023 Jul 10;15(7):e17159
pubmed: 37366158
Cell. 2000 Dec 22;103(7):1121-31
pubmed: 11163187
Nat Commun. 2015 Jul 03;6:7581
pubmed: 26138914
Biol Rev Camb Philos Soc. 2021 Feb;96(1):310-329
pubmed: 33089614
Nat Genet. 2004 Oct;36(10):1073-8
pubmed: 15448691
J Cell Sci. 2017 Sep 15;130(18):3009-3022
pubmed: 28743738
BMB Rep. 2017 Apr;50(4):175-185
pubmed: 28115040
Nat Commun. 2018 Sep 14;9(1):3752
pubmed: 30218034
Mol Cancer. 2021 Apr 29;20(1):72
pubmed: 33926465