Engineered transfer RNAs for suppression of premature termination codons.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
18 02 2019
18 02 2019
Historique:
received:
01
07
2018
accepted:
21
12
2018
entrez:
20
2
2019
pubmed:
20
2
2019
medline:
16
4
2019
Statut:
epublish
Résumé
Premature termination codons (PTCs) are responsible for 10-15% of all inherited disease. PTC suppression during translation offers a promising approach to treat a variety of genetic disorders, yet small molecules that promote PTC read-through have yielded mixed performance in clinical trials. Here we present a high-throughput, cell-based assay to identify anticodon engineered transfer RNAs (ACE-tRNA) which can effectively suppress in-frame PTCs and faithfully encode their cognate amino acid. In total, we identify ACE-tRNA with a high degree of suppression activity targeting the most common human disease-causing nonsense codons. Genome-wide transcriptome ribosome profiling of cells expressing ACE-tRNA at levels which repair PTC indicate that there are limited interactions with translation termination codons. These ACE-tRNAs display high suppression potency in mammalian cells, Xenopus oocytes and mice in vivo, producing PTC repair in multiple genes, including disease causing mutations within cystic fibrosis transmembrane conductance regulator (CFTR).
Identifiants
pubmed: 30778053
doi: 10.1038/s41467-019-08329-4
pii: 10.1038/s41467-019-08329-4
pmc: PMC6379413
doi:
Substances chimiques
CFTR protein, human
0
Codon, Nonsense
0
Cystic Fibrosis Transmembrane Conductance Regulator
126880-72-6
RNA, Transfer
9014-25-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
822Subventions
Organisme : NCI NIH HHS
ID : P30 CA010815
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK054759
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM106569
Pays : United States
Références
Nucleic Acids Res. 1993 Jul 1;21(13):3119-23
pubmed: 8332534
Hum Gene Ther. 1999 Sep 1;10(13):2209-19
pubmed: 10498252
Nucleic Acids Res. 1994 Apr 25;22(8):1327-34
pubmed: 8190621
Annu Rev Biochem. 2007;76:51-74
pubmed: 17352659
Proc Natl Acad Sci U S A. 1979 Jun;76(6):2886-9
pubmed: 88735
Nature. 2010 Sep 23;467(7314):470-3
pubmed: 20835226
Nucleic Acids Res. 2014 Mar;42(5):e37
pubmed: 24369425
Nature. 1991 Sep 19;353(6341):273-6
pubmed: 1832744
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
Nucleic Acids Res. 2016 Jul 8;44(W1):W54-7
pubmed: 27174935
Nucleic Acids Res. 1998 Jan 1;26(1):335-7
pubmed: 9399869
FEBS Lett. 2002 Mar 6;514(1):84-9
pubmed: 11904187
Nat Med. 1996 Apr;2(4):467-9
pubmed: 8597960
FEBS J. 2016 Apr;283(7):1218-31
pubmed: 26535798
Hum Mutat. 2002 Dec;20(6):439-46
pubmed: 12442267
Methods. 2002 Feb;26(2):105-14
pubmed: 12054887
Cancer Immunol Immunother. 2017 Dec;66(12):1577-1588
pubmed: 28819703
Nat Biotechnol. 2014 Mar;32(3):223-6
pubmed: 24727771
Hum Mutat. 2015 Apr;36(4):395-402
pubmed: 25604253
Nat Protoc. 2012 Jul 26;7(8):1534-50
pubmed: 22836135
Cell. 1981 Dec;27(3 Pt 2):543-53
pubmed: 6101206
J Clin Invest. 1998 Jul 15;102(2):361-70
pubmed: 9664077
J Biochem. 2003 Nov;134(5):751-8
pubmed: 14688241
Cell Rep. 2017 Aug 8;20(6):1463-1475
pubmed: 28793268
Wiley Interdiscip Rev RNA. 2014 Jul-Aug;5(4):461-80
pubmed: 24706556
Nucleic Acids Res. 2016 Jul 8;44(W1):W3-W10
pubmed: 27137889
J Mol Biol. 1971 Jun 14;58(2):439-58
pubmed: 4933412
RNA. 2000 Jul;6(7):1044-55
pubmed: 10917599
Cell. 1990 Nov 16;63(4):827-34
pubmed: 1699669
Nucleic Acids Res. 1997 Mar 1;25(5):955-64
pubmed: 9023104
Hum Mutat. 2000;15(1):45-51
pubmed: 10612821
Nucleic Acids Res. 1985 Sep 11;13(17):6265-72
pubmed: 2995924
Hum Mol Genet. 1996 Dec;5(12):2033-7
pubmed: 8968760
Cell. 1995 Jan 13;80(1):155-65
pubmed: 7813012
J Clin Invest. 2007 Dec;117(12):3952-7
pubmed: 18008009
Science. 2009 Apr 10;324(5924):218-23
pubmed: 19213877
Cell. 2014 Feb 27;156(5):950-62
pubmed: 24581494
ACS Chem Biol. 2016 Feb 19;11(2):400-8
pubmed: 26569370
Nucleic Acids Res. 1990 Nov 11;18(21):6339-45
pubmed: 2123028
Science. 2009 Jul 17;325(5938):336-9
pubmed: 19608921
EMBO J. 2000 Jan 17;19(2):306-14
pubmed: 10637234
Nature. 1979 Jan 11;277(5692):146-8
pubmed: 366438
Hear Res. 1994 Mar;73(2):173-84
pubmed: 7514588
Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2064-9
pubmed: 18272502
J Biol Chem. 2015 Jul 24;290(30):18454-66
pubmed: 26055716
Proc Natl Acad Sci U S A. 1989 Sep;86(17):6696-8
pubmed: 2505255
Am J Respir Cell Mol Biol. 2014 Apr;50(4):805-16
pubmed: 24251786
J Mol Biol. 1989 Apr 5;206(3):489-501
pubmed: 2469803
N Engl J Med. 2005 May 12;352(19):1992-2001
pubmed: 15888700
J Mol Biol. 2010 Feb 26;396(3):821-31
pubmed: 20026070
Annu Rev Genet. 2013;47:139-65
pubmed: 24274751
EMBO J. 1993 Aug;12(8):3315-22
pubmed: 8344267
Mol Ther Nucleic Acids. 2016;5:e349
pubmed: 28131272
Nature. 2004 Nov 4;432(7013):112-8
pubmed: 15525991
Nature. 2007 May 3;447(7140):87-91
pubmed: 17450125
Nat Genet. 1992 Oct;2(2):103-6
pubmed: 1303257
J Mol Biol. 1989 Apr 5;206(3):503-11
pubmed: 2469804
Proc Natl Acad Sci U S A. 2016 Nov 1;113(44):12508-12513
pubmed: 27702906
Exp Eye Res. 2006 Jul;83(1):97-119
pubmed: 16545802
Biochim Biophys Acta. 2009 Apr;1793(4):684-96
pubmed: 19111581
Mol Cell Biol. 2000 May;20(9):3116-24
pubmed: 10757796
Genet Anal. 1996 Dec;13(6):139-45
pubmed: 9117889
J Mol Biol. 1995 Aug 18;251(3):334-45
pubmed: 7650736
Microbiology. 2008 Sep;154(Pt 9):2814-2826
pubmed: 18757815
Nature. 1979 Jan 11;277(5692):148-50
pubmed: 366439
Nature. 1982 Apr 8;296(5857):537-40
pubmed: 6803169
Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8392-6
pubmed: 7690960