title: A nitric oxide regulated small RNA controls expression of genes involved in redox homeostasis in Bacillus subtilis.
abstract: RsaE is the only known trans-acting small regulatory RNA (sRNA) besides the ubiquitous 6S RNA that is conserved between the human pathogen Staphylococcus aureus and the soil-dwelling Firmicute Bacillus subtilis. Although a number of RsaE targets are known in S. aureus, neither the environmental signals that lead to its expression nor its physiological role are known. Here we show that expression of the B. subtilis homolog of RsaE is regulated by the presence of nitric oxide (NO) in the cellular milieu. Control of expression by NO is dependent on the ResDE two-component system in B. subtilis and we determined that the same is true in S. aureus. Transcriptome and proteome analyses revealed that many genes with functions related to oxidative stress and oxidation-reduction reactions were up-regulated in a B. subtilis strain lacking this sRNA. We have thus renamed it RoxS. The prediction of RoxS-dependent mRNA targets also suggested a significant enrichment for mRNAs related to respiration and electron transfer. Among the potential direct mRNA targets, we have validated the ppnKB mRNA, encoding an NAD+/NADH kinase, both in vivo and in vitro. RoxS controls both translation initiation and the stability of this transcript, in the latter case via two independent pathways implicating RNase Y and RNase III. Furthermore, RNase Y intervenes at an additional level by processing the 5' end of the RoxS sRNA removing about 20 nucleotides. Processing of RoxS allows it to interact more efficiently with a second target, the sucCD mRNA, encoding succinyl-CoA synthase, thus expanding the repertoire of targets recognized by this sRNA.
authors: CNRS FRE 3630 (affiliated with Univ. Paris Diderot, Sorbonne Paris Cité), Institut de Biologie Physico-Chimique, Paris, France.
authors: Sylvain
authors: S
authors: Durand
authors: CNRS FRE 3630 (affiliated with Univ. Paris Diderot, Sorbonne Paris Cité), Institut de Biologie Physico-Chimique, Paris, France.
authors: Frédérique
authors: F
authors: Braun
authors: Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, Strasbourg, France.
authors: Efthimia
authors: E
authors: Lioliou
authors: Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, Strasbourg, France.
authors: Cédric
authors: C
authors: Romilly
authors: Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, Strasbourg, France.
authors: Anne-Catherine
authors: AC
authors: Helfer
authors: Plateforme Protéomique Esplanade, IBMC, Strasbourg, France.
authors: Laurianne
authors: L
authors: Kuhn
authors: Mathématique Informatique et Génome, INRA UR1077, Jouy en Josas, France.
authors: Noé
authors: N
authors: Quittot
authors: Mathématique Informatique et Génome, INRA UR1077, Jouy en Josas, France.
authors: Pierre
authors: P
authors: Nicolas
authors: Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, Strasbourg, France.
authors: Pascale
authors: P
authors: Romby
authors: CNRS FRE 3630 (affiliated with Univ. Paris Diderot, Sorbonne Paris Cité), Institut de Biologie Physico-Chimique, Paris, France.
authors: Ciarán
authors: C
authors: Condon
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D006706:Homeostasis / Q000235:genetics; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D012329:RNA, Bacterial / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated / Q000096:biosynthesis / Q000235:genetics*; D043244:Ribonuclease III / Q000235:genetics; D013203:Staphylococcal Infections / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: C411065:6S RNA; D012329:RNA, Bacterial; D012333:RNA, Messenger; D022661:RNA, Untranslated; D009569:Nitric Oxide; D043244:Ribonuclease III
references: Braz J Med Biol Res. 1999 Nov;32(11):1417-27
references: 10559844
references: Science. 2009 Sep 11;325(5946):1380-4
references: 19745150
references: BMC Microbiol. 2008;8:128
references: 18662407
references: Cell. 2013 Feb 14;152(4):818-30
references: 23415229
references: Science. 2012 Mar 2;335(6072):1103-6
references: 22383849
references: Nucleic Acids Res. 2005;33(5):1678-89
references: 15781494
references: Nucleic Acids Res. 2012 Oct;40(19):9571-83
references: 22904090
references: Nature. 2014 Jun 12;510(7504):298-302
references: 24805240
references: EMBO J. 2010 Sep 15;29(18):3094-107
references: 20683441
references: Methods Mol Biol. 2012;905:227-34
references: 22736007
references: Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):1009-13
references: 18215992
references: Methods Mol Biol. 2009;540:247-63
references: 19381565
references: J Mol Biol. 2011 Feb 11;406(1):29-43
references: 21147125
references: Nucleic Acids Res. 2011 Apr;39(7):2918-30
references: 21138960
references: Mol Cell. 2011 Sep 16;43(6):880-91
references: 21925377
references: Cold Spring Harb Perspect Med. 2013 Sep;3(9):a010298
references: 24003243
references: J Mol Biol. 1990 Apr 5;212(3):461-71
references: 1691299
references: J Bacteriol. 1997 Dec;179(23):7251-6
references: 9393687
references: J Bacteriol. 2012 May;194(10):2594-605
references: 22389480
references: Cell. 2007 May 18;129(4):681-92
references: 17512403
references: Nucleic Acids Res. 2012 Nov 1;40(20):e156
references: 22821568
references: J Biol Chem. 2013 Mar 1;288(9):6417-26
references: 23322784
references: J Bacteriol. 2004 Oct;186(19):6477-84
references: 15375128
references: J Bacteriol. 2008 Jul;190(14):4997-5008
references: 18487332
references: Methods Enzymol. 2008;447:259-76
references: 19161848
references: Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):E3487-96
references: 23980183
references: Nucleic Acids Res. 2005;33(7):2141-52
references: 15831787
references: MBio. 2013;4(6):e00696-13
references: 24222487
references: PLoS One. 2014;9(6):e98661
references: 24932523
references: Mol Microbiol. 2010 Sep;77(6):1416-28
references: 20572941
references: Science. 2001 Jun 22;292(5525):2314-6
references: 11423658
references: PLoS One. 2012;7(5):e37294
references: 22629378
references: J Bacteriol. 2012 May;194(10):2586-93
references: 22427629
references: Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13855-60
references: 16172391
references: EMBO J. 2009 Nov 18;28(22):3523-33
references: 19779461
references: Methods Mol Biol. 2009;540:215-32
references: 19381563
references: Nucleic Acids Res. 2010 Oct;38(19):6620-36
references: 20511587
references: Anal Chem. 2005 Oct 1;77(19):6218-24
references: 16194081
references: Mol Microbiol. 2009 Oct;74(1):139-58
references: 19732340
references: Gene. 1995 Dec 29;167(1-2):335-6
references: 8566804
references: Stat Appl Genet Mol Biol. 2004;3:Article3
references: 16646809
references: J Biol Chem. 2007 Jan 26;282(4):2196-202
references: 17127770
references: PLoS One. 2013;8(2):e55156
references: 23457461
references: Nucleic Acids Res. 2011 Jul;39(Web Server issue):W149-54
references: 21672960
references: BMC Bioinformatics. 2008;9:303
references: 18613966
references: Nucleic Acids Res. 2012 Dec;40(22):11659-72
references: 23034808
references: PLoS Genet. 2012;8(3):e1002520
references: 22412379
references: RNA Biol. 2011 May-Jun;8(3):358-64
references: 21532344
references: Mol Microbiol. 2006 Oct;62(2):520-36
references: 17020585
references: Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11927-32
references: 18697947
references: Mol Microbiol. 2007 Jan;63(1):127-38
references: 17229210
references: J Bacteriol. 2013 Feb;195(3):534-44
references: 23175651
references: J Bacteriol. 2014 Jan;196(2):493-503
references: 24214949
references: Int J Artif Organs. 2010 Oct 5;:null
references: 20925037
references: Proc Natl Acad Sci U S A. 2010 May 25;107(21):9602-7
references: 20457943
references: Nucleic Acids Res. 2009 Nov;37(21):7239-57
references: 19786493
references: Mol Microbiol. 2007 Jul;65(2):373-85
references: 17590231
references: Proteomics. 2012 Jun;12(12):1928-37
references: 22623418
references: J Bacteriol. 2004 Apr;186(7):2028-37
references: 15028686
references: J Bacteriol. 2002 Mar;184(6):1783-7
references: 11872732
references: Mol Microbiol. 2010 Dec;78(6):1332-47
references: 21143309
references: Annu Rev Biochem. 2010;79:445-70
references: 20370423
references: Nat Struct Mol Biol. 2009 Aug;16(8):840-6
references: 19620966
references: EMBO J. 2005 Feb 23;24(4):824-35
references: 15678100
references: J Bacteriol. 2004 Mar;186(6):1694-704
references: 14996800
references: Genes Dev. 2014 Jul 15;28(14):1620-34
references: 25030700
references: J Bacteriol. 2000 Aug;182(16):4458-65
references: 10913079