title: Inducible suppression of global translation by overuse of rare codons.
abstract: Recently, artificial gene networks have been developed in synthetic biology to control gene expression and make organisms as controllable as robots. Here, I present an artificial posttranslational gene-silencing system based on the codon usage bias and low tRNA content corresponding to minor codons. I engineered the green fluorescent protein (GFP) gene to inhibit translation indirectly with the lowest-usage codons to monopolize various minor tRNAs (lgfp). The expression of lgfp interfered nonspecifically with the growth of Escherichia coli, Saccharomyces cerevisiae, human HeLa cervical cancer cells, MCF7 breast cancer cells, and HEK293 kidney cells, as well as phage and adenovirus expansion. Furthermore, insertion of lgfp downstream of a phage response promoter conferred phage resistance on E. coli. Such engineered gene silencers could act as components of biological networks capable of functioning with suitable promoters in E. coli, S. cerevisiae, and human cells to control gene expression. The results presented here show general suppressor artificial genes for live cells and viruses. This robust system provides a gene expression or cell growth control device for artificially synthesized gene networks.
authors: Japan Agency for Marine-Earth Science and Technology (JAMSTEC), Yokosuka, Japan hidekik@jamstec.go.jp.
authors: Hideki
authors: H
authors: Kobayashi
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000254:growth & development; D001435:Bacteriophages / Q000235:genetics / Q000254:growth & development; D002460:Cell Line; D003062:Codon; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development; D005786:Gene Expression Regulation; D020868:Gene Silencing; D017930:Genes, Reporter; D005813:Genes, Synthetic; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D017422:Sequence Analysis, DNA
chemical_list: D003062:Codon; D049452:Green Fluorescent Proteins
references: Hum Gene Ther. 2012 Sep;23(9):917-31
references: 22734618
references: Science. 2011 Sep 2;333(6047):1244-8
references: 21885772
references: Cell Rep. 2013 Jul 25;4(2):231-7
references: 23871664
references: Cell. 2014 Jul 3;158(1):110-20
references: 24995982
references: Nat Biotechnol. 2014 Dec;32(12):1276-81
references: 25402616
references: Nucleic Acids Res. 2000 Jan 1;28(1):292
references: 10592250
references: Nature. 2000 Jan 20;403(6767):335-8
references: 10659856
references: Nature. 2000 Jan 20;403(6767):339-42
references: 10659857
references: Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7963-8
references: 10859354
references: Nature. 2002 Nov 14;420(6912):224-30
references: 12432407
references: Nature. 2003 Apr 10;422(6932):633-7
references: 12687005
references: Bioinformatics. 2003 Nov 1;19(16):2005-15
references: 14594704
references: Nature. 2004 Apr 8;428(6983):617-24
references: 15004568
references: Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8414-9
references: 15159530
references: Nat Biotechnol. 2004 Jul;22(7):841-7
references: 15208640
references: Nature. 1970 Aug 15;227(5259):680-5
references: 5432063
references: Proc Natl Acad Sci U S A. 1973 May;70(5):1481-5
references: 4197092
references: J Gen Virol. 1977 Jul;36(1):59-74
references: 886304
references: J Mol Biol. 1981 Sep 25;151(3):389-409
references: 6175758
references: Mol Biol Evol. 1985 Jan;2(1):13-34
references: 3916708
references: Genetics. 1989 May;122(1):19-27
references: 2659436
references: Gene. 1989 Dec 21;85(1):109-14
references: 2515992
references: Nucleic Acids Res. 1991 Nov 25;19(22):6119-22
references: 1956771
references: Annu Rev Biophys Biomol Struct. 1992;21:441-83
references: 1525473
references: Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8000-4
references: 8367455
references: Science. 2011 Sep 2;333(6047):1248-52
references: 21885773
references: Gene. 1994 Oct 11;148(1):15-21
references: 7926828
references: J Bacteriol. 1996 May;178(10):2926-33
references: 8631683
references: Gene. 1996;173(1 Spec No):33-8
references: 8707053
references: J Mol Biol. 1996 Oct 4;262(4):407-12
references: 8893852
references: J Mol Biol. 1996 Oct 4;262(4):437-58
references: 8893855
references: Microbiology. 1997 Feb;143 ( Pt 2):303-11
references: 9043107
references: Mol Microbiol. 1997 Apr;24(2):255-61
references: 9159513
references: J Biol Chem. 1964 Dec;239:4182-5
references: 14247666
references: Trends Microbiol. 2005 May;13(5):236-42
references: 15866041
references: Nature. 2005 May 5;435(7038):118-22
references: 15875027
references: Cell. 2007 Jul 27;130(2):363-72
references: 17662949
references: Nat Biotechnol. 2007 Dec;25(12):1444-54
references: 18066041
references: Nature. 2008 Nov 27;456(7221):516-9
references: 18971928
references: Nature. 2009 Jan 15;457(7227):309-12
references: 19148099
references: Science. 2009 May 29;324(5931):1199-202
references: 19478183
references: Nat Rev Genet. 2010 May;11(5):367-79
references: 20395970
references: Cold Spring Harb Perspect Med. 2012 Oct;2(10). pii: a007179. doi: 10.1101/cshperspect.a007179
references: 23028130