Quantitative characteristics of gene regulation by small RNA.
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.
Levine
Erel
E
Center for Theoretical Biological Physics, University of California San Diego, La Jolla, California, United States of America.
Zhang
Zhongge
Z
Kuhlman
Thomas
T
Hwa
Terence
T
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
D034741:RNA, Small Interfering
Nat Rev Genet. 2005 Jun;6(6):451-64
15883588
Annu Rev Biochem. 2005;74:199-217
15952886
Trends Genet. 2005 Jul;21(7):399-404
15913835
Science. 2005 Sep 2;309(5740):1519-24
16141061
Genes Dev. 2005 Sep 15;19(18):2176-86
16166379
J Bacteriol. 2005 Oct;187(20):6962-71
16199566
Dev Biol. 2006 Jan 1;289(1):3-16
16325172
Nature. 2006 Mar 16;440(7082):358-62
16541077
Science. 2006 Mar 17;311(5767):1600-3
16543458
Nucleic Acids Res. 2006;34(7):e52
16614443
Nat Genet. 2006 Jun;38 Suppl:S20-4
16736020
Mol Microbiol. 2006 Aug;61(4):1013-22
16859494
Mol Microbiol. 2006 Nov;62(4):1181-90
17078818
J Bacteriol. 2007 Mar;189(5):1963-73
17158661
Nucleic Acids Res. 2007;35(3):1018-37
17264113
Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):6043-8
17376875
Curr Opin Microbiol. 2007 Apr;10(2):134-9
17383928
Nature. 2004 Sep 16;431(7006):350-5
15372042
Biochem Biophys Res Commun. 2004 Oct 22;323(3):1017-23
15381101
J Bacteriol. 2004 Oct;186(20):6689-97
15466019
Mol Microbiol. 2003 May;48(4):855-61
12753181
FEMS Microbiol Rev. 2003 Jun;27(2-3):215-37
12829269
Genes Dev. 2003 Oct 1;17(19):2374-83
12975324
RNA. 2003 Nov;9(11):1308-14
14561880
Nucleic Acids Res. 2003 Nov 15;31(22):6435-43
14602901
Mol Microbiol. 2003 Nov;50(4):1111-24
14622403
Cell. 2004 Jan 23;116(2):281-97
14744438
J Bacteriol. 2004 Oct;186(20):6698-705
15466020
Annu Rev Microbiol. 2004;58:303-28
15487940
Biochemistry. 1976 Mar 9;15(5):1165-71
3211
J Mol Biol. 1979 Jul 5;131(3):573-92
390161
Proc Natl Acad Sci U S A. 1980 May;77(5):2450-4
6156450
Nature. 1981 Dec 17;294(5842):623-6
6171736
Proc Natl Acad Sci U S A. 1981 Oct;78(10):6008-12
6171808
Proc Natl Acad Sci U S A. 1981 Nov;78(11):6840-4
6947258
Cell. 1983 Sep;34(2):673-82
6311437
Cell. 1983 Sep;34(2):683-91
6311438
Cell. 1985 Nov;43(1):117-30
3000598
Proc Natl Acad Sci U S A. 1986 Mar;83(6):1787-91
3006072
J Bacteriol. 1987 Jul;169(7):3007-12
2439487
Gene. 1988 Dec 10;72(1-2):219-36
2468561
EMBO J. 1989 Dec 20;8(13):4297-305
2480235
EMBO J. 1990 Apr;9(4):1259-66
1691096
EMBO J. 1990 Apr;9(4):1267-74
1691097
EMBO J. 1990 Jul;9(7):2331-40
1694128
Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):405-9
1703297
Annu Rev Cell Biol. 1990;6:297-327
2177342
Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3338-42
1565624
Plasmid. 1992 Jul;28(1):14-24
1387714
Nucleic Acids Res. 1992 Dec 25;20(24):6723-32
1282705
Mol Microbiol. 1993 Jul;9(2):233-47
7692216
Annu Rev Microbiol. 1994;48:713-42
7826024
Nucleic Acids Res. 1995 Feb 25;23(4):580-7
7534907
Gene. 1996;173(1 Spec No):33-8
8707053
J Mol Biol. 1999 Dec 17;294(5):1115-25
10600370
Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5
10829079
J Mol Biol. 2000 Jul 28;300(5):1101-12
10903857
Nat Biotechnol. 2000 Dec;18(12):1262-8
11101804
J Bacteriol. 2001 Mar;183(6):1997-2005
11222598
Genes Dev. 2001 Jul 1;15(13):1637-51
11445539
Curr Biol. 2001 Jun 26;11(12):941-50
11448770
J Mol Biol. 2001 Jul 27;310(5):1125-34
11502000
Curr Biol. 2001 Sep 4;11(17):1369-73
11553332
J Bacteriol. 2001 Dec;183(23):6752-62
11698362
Mol Cell. 2002 Jan;9(1):11-22
11804582
Mol Cell. 2002 Jan;9(1):23-30
11804583
EMBO J. 1983;2(1):93-8
11894917
Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4620-5
11917098
Adv Genet. 2002;46:361-98
11931231
Nat Genet. 2002 May;31(1):69-73
11967532
Nucleic Acids Res. 2002 Sep 1;30(17):3732-8
12202758
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12795-800
12237400
Biophys J. 2003 Jan;84(1):154-70
12524272
Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5136-41
12702751
EMBO J. 2004 Jan 28;23(2):396-405
14739933
Curr Opin Microbiol. 2004 Apr;7(2):140-4
15063850
Nat Rev Genet. 2004 May;5(5):396-400
15143321
Nat Biotechnol. 2004 Jul;22(7):841-7
15208640
Cell. 2004 Jul 9;118(1):69-82
15242645
J Bacteriol. 2004 Sep;186(18):6179-85
15342588
Nucleic Acids Res. 1997 Mar 15;25(6):1203-10
9092630
Annu Rev Genet. 1997;31:1-31
9442888
Mol Microbiol. 2004 Nov;54(4):1076-89
15522088
J Mol Biol. 2004 Dec 3;344(4):965-76
15544806
Curr Biol. 2004 Dec 29;14(24):2271-6
15620655
J Bacteriol. 2005 Feb;187(3):980-90
15659676
Nucleic Acids Res. 2005;33(3):1040-50
15718303
Curr Opin Genet Dev. 2005 Apr;15(2):116-24
15797194
Curr Opin Genet Dev. 2005 Apr;15(2):125-35
15797195
Crit Rev Biochem Mol Biol. 2005 Mar-Apr;40(2):93-113
15814430