An antisense RNA that governs the expression kinetics of a multifunctional virulence gene.
Genome-wide transcriptome analyses of several bacterial species have recently uncovered a hitherto unappreciated amount of antisense transcription. However, the physiological role, regulation and significance of such antisense transcripts are presently unclear. We now report the identification of a cis-encoded 1.2 kb long antisense RNA - termed AmgR - that is complementary to the mgtC portion of the mgtCBR polycistronic message from Salmonella enterica. The mgtCBR mRNA specifies the MgtC protein, which is necessary for survival within macrophages, virulence in mice and growth in low Mg(2+); the Mg(2+) transporter MgtB with no apparent role in virulence; and the membrane peptide MgtR mediating MgtC degradation. Expression of AmgR diminished both MgtC and MgtB protein levels in a process requiring RNase E but independent of RNase III, the RNA chaperone Hfq, and the regulatory peptide MgtR. Inactivation of the chromosomal amgR promoter increased MgtC and MgtB protein levels and enhanced Salmonella virulence. Surprisingly, AmgR transcription is governed by the regulatory protein PhoP, which also directs transcription of the sense mgtCBR mRNA. AmgR may function as a timing device that alters MgtC and MgtB levels after the onset of PhoP-inducing conditions.
Lee
Eun-Jin
EJ
Department of Molecular Microbiology, Howard Hughes Medical Institute, Washington University School of Medicine, Campus Box 8230, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
Groisman
Eduardo A
EA
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D020871:RNA Stability; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D016372:RNA, Antisense; C061064:PhoP protein, Bacteria; D000251:Adenosine Triphosphatases; C083836:MgtB protein, Salmonella typhimurium; C093586:MgtC protein, Salmonella typhimurium
PLoS Biol. 2008 Mar 18;6(3):e64
18351803
Genes Dev. 2009 Sep 1;23(17):2004-15
19638370
J Bacteriol. 1996 Sep;178(17):5092-9
8752324
Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2862-7
15703297
Nature. 2009 Jun 18;459(7249):950-6
19448609
PLoS Pathog. 2006 Feb;2(2):e11
16518469
Mol Microbiol. 2000 Mar;35(6):1375-82
10760138
J Bacteriol. 1995 Aug;177(15):4364-71
7543474
Genes Dev. 1990 Dec;4(12A):2223-33
2148537
Trends Genet. 2002 May;18(5):223-6
12047936
Nature. 2010 Mar 11;464(7286):250-5
20164839
Mol Microbiol. 2007 Jan;63(2):605-22
17176255
Infect Immun. 2005 May;73(5):3160-3
15845525
Curr Opin Microbiol. 2007 Apr;10(2):110-6
17376732
PLoS One. 2009 Oct 19;4(10):e7526
19838305
Curr Opin Microbiol. 2007 Apr;10(2):117-24
17376733
Cell. 2003 Oct 31;115(3):333-42
14636560
Cell. 2006 Apr 7;125(1):71-84
16615891
Science. 2005 Sep 2;309(5740):1564-6
16141073
Curr Opin Microbiol. 2007 Jun;10(3):257-61
17553733
J Mol Biol. 2007 Oct 26;373(3):521-8
17854828
Mol Microbiol. 2002 Apr;44(2):561-71
11972791
Curr Opin Microbiol. 2007 Apr;10(2):102-9
17387036
J Bacteriol. 2009 Feb;191(3):1101-5
19047346
Nucleic Acids Res. 2006 Feb 01;34(2):659-66
16452296
Cell. 2009 Feb 20;136(4):615-28
19239884
J Bacteriol. 1990 May;172(5):2485-90
2185222
J Mol Evol. 2003 Oct;57(4):479-86
14708580
Microbiol Mol Biol Rev. 2008 Dec;72(4):579-89, Table of Contents
19052321
Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8754-61
10922031
FEMS Microbiol Lett. 2008 Mar;280(2):226-34
18248433
Science. 2006 Dec 8;314(5805):1607-9
17158330
EMBO J. 2009 Jun 3;28(11):1551-61
19407815
J Bacteriol. 2007 May;189(9):3479-88
17337574
Trends Microbiol. 2007 Jun;15(6):252-6
17416526
Gene. 1985;33(1):103-19
2985470
Genes Dev. 2002 Jul 1;16(13):1696-706
12101127
Mol Microbiol. 2008 Apr;68(2):298-313
18383615
Genes Dev. 2004 Sep 15;18(18):2302-13
15371344
Science. 1989 Feb 24;243(4894 Pt 1):1059-62
2646710
J Biol Chem. 2004 Sep 10;279(37):38618-25
15208313
Microbiology (Reading). 1998 Jul;144 ( Pt 7):1835-1843
9695916
Nucleic Acids Res. 2004 Sep 08;32(16):4812-20
15356298
Mol Microbiol. 2004 Oct;54(2):386-95
15469511
Proc Natl Acad Sci U S A. 2006 Sep 5;103(36):13503-8
16938894
Nucleic Acids Res. 2009 Apr;37(6):e46
19223322
J Bacteriol. 1981 Feb;145(2):1110-1
7007341
Infect Immun. 2006 Jul;74(7):3727-41
16790745
Proc Natl Acad Sci U S A. 1986 Jul;83(14):5189-93
3523484
Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5
10829079
J Biol Chem. 2005 Feb 11;280(6):4089-94
15569664
PLoS One. 2009;4(5):e5551
19436747
Infect Immun. 2006 Oct;74(10):5477-86
16988222
J Mol Biol. 1983 Jun 5;166(4):557-80
6345791
Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7794-9
8755555
Biol Chem. 2005 Dec;386(12):1219-38
16336117
Biochim Biophys Acta. 2002 May 3;1575(1-3):15-25
12020814
Infect Immun. 2004 Aug;72(8):4654-61
15271926
Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4706-11
12676988
EMBO J. 1997 Sep 1;16(17):5376-85
9311997
Mol Microbiol. 1995 Aug;17(4):747-56
8801428
Annu Rev Biochem. 2005;74:199-217
15952886
Cell. 1996 Jan 12;84(1):165-74
8548821
Mol Microbiol. 2005 Jul;57(1):85-96
15948951
Mol Microbiol. 2009 Dec;74(6):1314-30
19889087
J Biol Chem. 1991 Jan 15;266(2):815-23
1824701
Nucleic Acids Res. 2008 Oct;36(18):5955-69
18812398
EMBO J. 2008 Feb 6;27(3):546-57
18200043
J Bacteriol. 1995 Jul;177(14):4121-30
7608087