title: Quantitative characteristics of gene regulation by small RNA.
abstract: An increasing number of small RNAs (sRNAs) have been shown to regulate critical pathways in prokaryotes and eukaryotes. In bacteria, regulation by trans-encoded sRNAs is predominantly found in the coordination of intricate stress responses. The mechanisms by which sRNAs modulate expression of its targets are diverse. In common to most is the possibility that interference with the translation of mRNA targets may also alter the abundance of functional sRNAs. Aiming to understand the unique role played by sRNAs in gene regulation, we studied examples from two distinct classes of bacterial sRNAs in Escherichia coli using a quantitative approach combining experiment and theory. Our results demonstrate that sRNA provides a novel mode of gene regulation, with characteristics distinct from those of protein-mediated gene regulation. These include a threshold-linear response with a tunable threshold, a robust noise resistance characteristic, and a built-in capability for hierarchical cross-talk. Knowledge of these special features of sRNA-mediated regulation may be crucial toward understanding the subtle functions that sRNAs can play in coordinating various stress-relief pathways. Our results may also help guide the design of synthetic genetic circuits that have properties difficult to attain with protein regulators alone.
authors: Center for Theoretical Biological Physics, University of California San Diego, La Jolla, California, United States of America.
authors: Erel
authors: E
authors: Levine
authors: Zhongge
authors: Z
authors: Zhang
authors: Thomas
authors: T
authors: Kuhlman
authors: Terence
authors: T
authors: Hwa
mesh_terms: D001419:Bacteria / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D034741:RNA, Small Interfering / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering
references: Nat Rev Genet. 2005 Jun;6(6):451-64
references: 15883588
references: Annu Rev Biochem. 2005;74:199-217
references: 15952886
references: Trends Genet. 2005 Jul;21(7):399-404
references: 15913835
references: Science. 2005 Sep 2;309(5740):1519-24
references: 16141061
references: Genes Dev. 2005 Sep 15;19(18):2176-86
references: 16166379
references: J Bacteriol. 2005 Oct;187(20):6962-71
references: 16199566
references: Dev Biol. 2006 Jan 1;289(1):3-16
references: 16325172
references: Nature. 2006 Mar 16;440(7082):358-62
references: 16541077
references: Science. 2006 Mar 17;311(5767):1600-3
references: 16543458
references: Nucleic Acids Res. 2006;34(7):e52
references: 16614443
references: Nat Genet. 2006 Jun;38 Suppl:S20-4
references: 16736020
references: Mol Microbiol. 2006 Aug;61(4):1013-22
references: 16859494
references: Mol Microbiol. 2006 Nov;62(4):1181-90
references: 17078818
references: J Bacteriol. 2007 Mar;189(5):1963-73
references: 17158661
references: Nucleic Acids Res. 2007;35(3):1018-37
references: 17264113
references: Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):6043-8
references: 17376875
references: Curr Opin Microbiol. 2007 Apr;10(2):134-9
references: 17383928
references: Nature. 2004 Sep 16;431(7006):350-5
references: 15372042
references: Biochem Biophys Res Commun. 2004 Oct 22;323(3):1017-23
references: 15381101
references: J Bacteriol. 2004 Oct;186(20):6689-97
references: 15466019
references: Mol Microbiol. 2003 May;48(4):855-61
references: 12753181
references: FEMS Microbiol Rev. 2003 Jun;27(2-3):215-37
references: 12829269
references: Genes Dev. 2003 Oct 1;17(19):2374-83
references: 12975324
references: RNA. 2003 Nov;9(11):1308-14
references: 14561880
references: Nucleic Acids Res. 2003 Nov 15;31(22):6435-43
references: 14602901
references: Mol Microbiol. 2003 Nov;50(4):1111-24
references: 14622403
references: Cell. 2004 Jan 23;116(2):281-97
references: 14744438
references: J Bacteriol. 2004 Oct;186(20):6698-705
references: 15466020
references: Annu Rev Microbiol. 2004;58:303-28
references: 15487940
references: Biochemistry. 1976 Mar 9;15(5):1165-71
references: 3211
references: J Mol Biol. 1979 Jul 5;131(3):573-92
references: 390161
references: Proc Natl Acad Sci U S A. 1980 May;77(5):2450-4
references: 6156450
references: Nature. 1981 Dec 17;294(5842):623-6
references: 6171736
references: Proc Natl Acad Sci U S A. 1981 Oct;78(10):6008-12
references: 6171808
references: Proc Natl Acad Sci U S A. 1981 Nov;78(11):6840-4
references: 6947258
references: Cell. 1983 Sep;34(2):673-82
references: 6311437
references: Cell. 1983 Sep;34(2):683-91
references: 6311438
references: Cell. 1985 Nov;43(1):117-30
references: 3000598
references: Proc Natl Acad Sci U S A. 1986 Mar;83(6):1787-91
references: 3006072
references: J Bacteriol. 1987 Jul;169(7):3007-12
references: 2439487
references: Gene. 1988 Dec 10;72(1-2):219-36
references: 2468561
references: EMBO J. 1989 Dec 20;8(13):4297-305
references: 2480235
references: EMBO J. 1990 Apr;9(4):1259-66
references: 1691096
references: EMBO J. 1990 Apr;9(4):1267-74
references: 1691097
references: EMBO J. 1990 Jul;9(7):2331-40
references: 1694128
references: Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):405-9
references: 1703297
references: Annu Rev Cell Biol. 1990;6:297-327
references: 2177342
references: Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3338-42
references: 1565624
references: Plasmid. 1992 Jul;28(1):14-24
references: 1387714
references: Nucleic Acids Res. 1992 Dec 25;20(24):6723-32
references: 1282705
references: Mol Microbiol. 1993 Jul;9(2):233-47
references: 7692216
references: Annu Rev Microbiol. 1994;48:713-42
references: 7826024
references: Nucleic Acids Res. 1995 Feb 25;23(4):580-7
references: 7534907
references: Gene. 1996;173(1 Spec No):33-8
references: 8707053
references: J Mol Biol. 1999 Dec 17;294(5):1115-25
references: 10600370
references: Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5
references: 10829079
references: J Mol Biol. 2000 Jul 28;300(5):1101-12
references: 10903857
references: Nat Biotechnol. 2000 Dec;18(12):1262-8
references: 11101804
references: J Bacteriol. 2001 Mar;183(6):1997-2005
references: 11222598
references: Genes Dev. 2001 Jul 1;15(13):1637-51
references: 11445539
references: Curr Biol. 2001 Jun 26;11(12):941-50
references: 11448770
references: J Mol Biol. 2001 Jul 27;310(5):1125-34
references: 11502000
references: Curr Biol. 2001 Sep 4;11(17):1369-73
references: 11553332
references: J Bacteriol. 2001 Dec;183(23):6752-62
references: 11698362
references: Mol Cell. 2002 Jan;9(1):11-22
references: 11804582
references: Mol Cell. 2002 Jan;9(1):23-30
references: 11804583
references: EMBO J. 1983;2(1):93-8
references: 11894917
references: Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4620-5
references: 11917098
references: Adv Genet. 2002;46:361-98
references: 11931231
references: Nat Genet. 2002 May;31(1):69-73
references: 11967532
references: Nucleic Acids Res. 2002 Sep 1;30(17):3732-8
references: 12202758
references: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12795-800
references: 12237400
references: Biophys J. 2003 Jan;84(1):154-70
references: 12524272
references: Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5136-41
references: 12702751
references: EMBO J. 2004 Jan 28;23(2):396-405
references: 14739933
references: Curr Opin Microbiol. 2004 Apr;7(2):140-4
references: 15063850
references: Nat Rev Genet. 2004 May;5(5):396-400
references: 15143321
references: Nat Biotechnol. 2004 Jul;22(7):841-7
references: 15208640
references: Cell. 2004 Jul 9;118(1):69-82
references: 15242645
references: J Bacteriol. 2004 Sep;186(18):6179-85
references: 15342588
references: Nucleic Acids Res. 1997 Mar 15;25(6):1203-10
references: 9092630
references: Annu Rev Genet. 1997;31:1-31
references: 9442888
references: Mol Microbiol. 2004 Nov;54(4):1076-89
references: 15522088
references: J Mol Biol. 2004 Dec 3;344(4):965-76
references: 15544806
references: Curr Biol. 2004 Dec 29;14(24):2271-6
references: 15620655
references: J Bacteriol. 2005 Feb;187(3):980-90
references: 15659676
references: Nucleic Acids Res. 2005;33(3):1040-50
references: 15718303
references: Curr Opin Genet Dev. 2005 Apr;15(2):116-24
references: 15797194
references: Curr Opin Genet Dev. 2005 Apr;15(2):125-35
references: 15797195
references: Crit Rev Biochem Mol Biol. 2005 Mar-Apr;40(2):93-113
references: 15814430