Small regulatory RNAs from low-GC Gram-positive bacteria

Small regulatory RNAs (sRNAs) that act by base-pairing were first discovered in so-called accessory DNA elements—plasmids, phages, and transposons—where they control replication, maintenance, and transposition. Since 2001, a huge body of work has been performed to predict and identify sRNAs in a multitude of bacterial genomes. The majority of chromosome-encoded sRNAs have been investigated in E. coli and other Gram-negative bacteria. However, during the past five years an increasing number of sRNAs were found in Gram-positive bacteria. Here, we outline our current knowledge on chromosome-encoded sRNAs from low-GC Gram-positive species that act by base-pairing, i.e., an antisense mechanism. We will focus on sRNAs with known targets and defined regulatory mechanisms with special emphasis on Bacillus subtilis.

[1]  P. Bouloc,et al.  No detectable effect of RNA-binding protein Hfq absence in Staphylococcus aureus , 2007, BMC Microbiology.

[2]  P. Bouloc,et al.  Lack of interchangeability of Hfq-like proteins. , 2012, Biochimie.

[3]  C. Condon,et al.  The Essential Function of B. subtilis RNase III Is to Silence Foreign Toxin Genes , 2012, PLoS genetics.

[4]  Fuli Li,et al.  RNA-seq-based comparative transcriptome analysis of the syngas-utilizing bacterium Clostridium ljungdahlii DSM 13528 grown autotrophically and heterotrophically. , 2013, Molecular bioSystems.

[5]  J. Vogel,et al.  Hfq and its constellation of RNA , 2011, Nature Reviews Microbiology.

[6]  S. Grewal.  RNAi-dependent formation of heterochromatin and its diverse functions. , 2010, Current opinion in genetics & development.

[7]  S. Brantl.  Acting antisense: plasmid- and chromosome-encoded sRNAs from Gram-positive bacteria. , 2012, Future microbiology.

[8]  R. Sorek,et al.  The excludon: a new concept in bacterial antisense RNA-mediated gene regulation , 2012, Nature Reviews Microbiology.

[9]  Uwe Sauer,et al.  A Global Investigation of the Bacillus subtilis Iron-Sparing Response Identifies Major Changes in Metabolism , 2012, Journal of bacteriology.

[10]  Martin Wagner,et al.  Listeria monocytogenes , 2014, Methods in Molecular Biology.

[11]  J. Vogel,et al.  An antisense RNA inhibits translation by competing with standby ribosomes. , 2007, Molecular cell.

[12]  J. Helmann,et al.  Extracytoplasmic Function σ Factors Regulate Expression of the Bacillus subtilis yabE Gene via a cis-Acting Antisense RNA , 2008, Journal of bacteriology.

[13]  I. Nes,et al.  Identification of the streptococcal competence‐pheromone receptor , 1996, Molecular microbiology.

[14]  S. Brantl.  Regulatory mechanisms employed by cis-encoded antisense RNAs. , 2007, Current opinion in microbiology.

[15]  S. Brantl.  Bacterial chromosome-encoded small regulatory RNAs. , 2009, Future microbiology.

[16]  Kayo Okumura,et al.  Characterization of Genes Regulated Directly by the VirR/VirS System in Clostridium perfringens , 2008, Journal of bacteriology.

[17]  B. Kallipolitis,et al.  Identification of small Hfq-binding RNAs in Listeria monocytogenes. , 2006, RNA.

[18]  K. Inokuchi,et al.  Mobile Genetic Element SCCmec-encoded psm-mec RNA Suppresses Translation of agrA and Attenuates MRSA Virulence , 2013, PLoS pathogens.

[19]  Haipeng Sun,et al.  ArtR, a novel sRNA of Staphylococcus aureus, regulates α-toxin expression by targeting the 5′ UTR of sarT mRNA , 2013, Medical Microbiology and Immunology.

[20]  B. Felden,et al.  A Staphylococcus aureus Small RNA Is Required for Bacterial Virulence and Regulates the Expression of an Immune-Evasion Molecule , 2010, PLoS pathogens.

[21]  Pascale Cossart,et al.  The non-coding RNA world of the bacterial pathogen Listeria monocytogenes , 2012, RNA biology.

[22]  S. Rasmussen,et al.  The transcriptionally active regions in the genome of Bacillus subtilis , 2009, Molecular microbiology.

[23]  J. Helmann,et al.  The Bacillus subtilis iron-sparing response is mediated by a Fur-regulated small RNA and three small, basic proteins , 2008, Proceedings of the National Academy of Sciences.

[24]  S. Kuhara,et al.  Unique Regulatory Mechanism of Sporulation and Enterotoxin Production in Clostridium perfringens , 2013, Journal of bacteriology.

[25]  B. Kallipolitis,et al.  Defining a role for Hfq in Gram-positive bacteria: evidence for Hfq-dependent antisense regulation in Listeria monocytogenes , 2009, Nucleic acids research.

[26]  L. Ponnala,et al.  Deep RNA sequencing of L. monocytogenes reveals overlapping and extensive stationary phase and sigma B-dependent transcriptomes, including multiple highly transcribed noncoding RNAs , 2009, BMC Genomics.

[27]  F. Vandenesch,et al.  Probing the structure of RNAIII, the Staphylococcus aureus agr regulatory RNA, and identification of the RNA domain involved in repression of protein A expression. , 2000, RNA.

[28]  R. Losick,et al.  Small Genes under Sporulation Control in the Bacillus subtilis genome , 2010, Journal of bacteriology.

[29]  J. Helmann,et al.  The FsrA sRNA and FbpB Protein Mediate the Iron-Dependent Induction of the Bacillus subtilis LutABC Iron-Sulfur-Containing Oxidases , 2012, Journal of bacteriology.

[30]  Kathryn J. Boor,et al.  A Small RNA Controls Expression of the Chitinase ChiA in Listeria monocytogenes , 2011, PloS one.

[31]  U. Gerth,et al.  The small untranslated RNA SR1 from the Bacillus subtilis genome is involved in the regulation of arginine catabolism , 2006, Molecular microbiology.

[32]  S. Brantl,et al.  Implication of CcpN in the regulation of a novel untranslated RNA (SR1) in Bacillus subtilis , 2005, Molecular microbiology.

[33]  Jessica M. Silvaggi,et al.  Small Untranslated RNA Antitoxin in Bacillus subtilis , 2005, Journal of bacteriology.

[34]  H. Kakeshita,et al.  Novel small RNA-encoding genes in the intergenic regions of Bacillus subtilis. , 2009, Gene.

[35]  J. Elf,et al.  RNAs actively cycle on the Sm-like protein Hfq. , 2010, Genes & development.

[36]  D. T. Jones,et al.  Studies on Clostridium acetobutylicum ginA promoters and antisense RNA , 1990, Molecular microbiology.

[37]  R. Hakenbeck,et al.  Effect of new alleles of the histidine kinase gene ciaH on the activity of the response regulator CiaR in Streptococcus pneumoniae R6. , 2011, Microbiology.

[38]  Sylvain Durand,et al.  Type I toxin-antitoxin systems in Bacillus subtilis , 2012, RNA biology.

[39]  F. Vandenesch,et al.  Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence factors and the transcription regulator Rot by an antisense mechanism. , 2007, Genes & development.

[40]  Andrew L. Feig,et al.  Identification and Characterization of Noncoding Small RNAs in Streptococcus pneumoniae Serotype 2 Strain D39 , 2009, Journal of bacteriology.

[41]  S. Saha,et al.  RNA Expression Analysis Using an AntisenseBacillus subtilis Genome Array , 2001, Journal of bacteriology.

[42]  B. Felden,et al.  Small RNA genes expressed from Staphylococcus aureus genomic and pathogenicity islands with specific expression among pathogenic strains. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[43]  J. Vogel,et al.  Identification of regulatory RNAs in Bacillus subtilis , 2010, Nucleic acids research.

[44]  R. Hakenbeck,et al.  Identification of the genes directly controlled by the response regulator CiaR in Streptococcus pneumoniae: five out of 15 promoters drive expression of small non‐coding RNAs , 2007, Molecular microbiology.

[45]  D. Gautheret,et al.  SINGLE‐PASS CLASSIFICATION OF ALL NON‐CODING SEQUENCES IN A BACTERIAL GENOME USING PHYLOGENETIC PROFILES , 2009, Genome research.

[46]  M. Sebert,et al.  The HtrA Protease from Streptococcus pneumoniae Digests Both Denatured Proteins and the Competence-stimulating Peptide* , 2012, The Journal of Biological Chemistry.

[47]  D. Gautheret,et al.  CsfG, a sporulation-specific, small non-coding RNA highly conserved in endospore formers , 2011, RNA biology.

[48]  C. Buchrieser,et al.  A trans-Acting Riboswitch Controls Expression of the Virulence Regulator PrfA in Listeria monocytogenes , 2009, Cell.

[49]  S. Hinrichs,et al.  Characterization of SSR42, a Novel Virulence Factor Regulatory RNA That Contributes to the Pathogenesis of a Staphylococcus aureus USA300 Representative , 2012, Journal of bacteriology.

[50]  E. Charpentier,et al.  Small RNAs in streptococci , 2012, RNA biology.

[51]  P. Romby,et al.  An overview of RNAs with regulatory functions in gram-positive bacteria , 2009, Cellular and Molecular Life Sciences.

[52]  Á. Zaballos,et al.  Identification of 88 regulatory small RNAs in the TIGR4 strain of the human pathogen Streptococcus pneumoniae. , 2012, RNA.

[53]  S. Brantl,et al.  Transcriptional repressor CcpN from Bacillus subtilis compensates asymmetric contact distribution by cooperative binding. , 2006, Journal of molecular biology.

[54]  F. Vandenesch,et al.  Staphylococcus aureus RNAIII Binds to Two Distant Regions of coa mRNA to Arrest Translation and Promote mRNA Degradation , 2010, PLoS pathogens.

[55]  Jie Dong,et al.  Hfq Is a Global Regulator That Controls the Pathogenicity of Staphylococcus aureus , 2010, PloS one.

[56]  Thomas Hartsch,et al.  Genome-Wide Identification of Small RNAs in the Opportunistic Pathogen Enterococcus faecalis V583 , 2011, PloS one.

[57]  S. Brantl.  Bacterial type I toxin-antitoxin systems , 2012, RNA biology.

[58]  R. Golbik,et al.  Identification of ligands affecting the activity of the transcriptional repressor CcpN from Bacillus subtilis. , 2008, Journal of molecular biology.

[59]  E. Papoutsakis,et al.  The Clostridium small RNome that responds to stress: the paradigm and importance of toxic metabolite stress in C. acetobutylicum , 2013, BMC Genomics.

[60]  I. Moll,et al.  In vitro analysis of the interaction between the small RNA SR1 and its primary target ahrC mRNA , 2007, Nucleic acids research.

[61]  Pascale Cossart,et al.  Identification of new noncoding RNAs in Listeria monocytogenes and prediction of mRNA targets , 2007, Nucleic acids research.

[62]  R. Hakenbeck,et al.  A two‐component signal‐transducing system is involved in competence and penicillin susceptibility in laboratory mutants of Streptococcus pneumoniae , 1994, Molecular microbiology.

[63]  David Hernández,et al.  Cartography of Methicillin-Resistant S. aureus Transcripts: Detection, Orientation and Temporal Expression during Growth Phase and Stress Conditions , 2010, PloS one.

[64]  J. Vogel,et al.  CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III , 2011, Nature.

[65]  S. Brantl,et al.  One antitoxin—two functions: SR4 controls toxin mRNA decay and translation , 2013, Nucleic acids research.

[66]  S. Brantl.  Antisense RNAs in plasmids: control of replication and maintenance. , 2002, Plasmid.

[67]  D. Morrison,et al.  An unmodified heptadecapeptide pheromone induces competence for genetic transformation in Streptococcus pneumoniae. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[68]  June R. Scott,et al.  RivR and the small RNA RivX: the missing links between the CovR regulatory cascade and the Mga regulon , 2007, Molecular microbiology.

[69]  J. Coppee,et al.  Genome-Wide Identification of Regulatory RNAs in the Human Pathogen Clostridium difficile , 2013, PLoS genetics.

[70]  Kouji Nakamura,et al.  A Novel Toxin Regulator, the CPE1446-CPE1447 Protein Heteromeric Complex, Controls Toxin Genes in Clostridium perfringens , 2011, Journal of bacteriology.

[71]  Kyu Hong Cho,et al.  Novel Regulatory Small RNAs in Streptococcus pyogenes , 2013, PloS one.

[72]  M. Nuhn,et al.  Identification of genes for small non-coding RNAs that belong to the regulon of the two-component regulatory system CiaRH in Streptococcus , 2010, BMC Genomics.

[73]  P. François,et al.  A search for small noncoding RNAs in Staphylococcus aureus reveals a conserved sequence motif for regulation , 2009, Nucleic acids research.

[74]  H. Hayashi,et al.  Identification of a novel locus that regulates expression of toxin genes in Clostridium perfringens. , 2002, FEMS microbiology letters.

[75]  Pascale Cossart,et al.  Comparative transcriptomics of pathogenic and non-pathogenic Listeria species , 2012, Molecular systems biology.

[76]  M. Vergassola,et al.  The Listeria transcriptional landscape from saprophytism to virulence , 2009, Nature.

[77]  E. Charpentier,et al.  Synthesis of group A streptococcal virulence factors is controlled by a regulatory RNA molecule , 2004, Molecular microbiology.

[78]  Bindu Nanduri,et al.  Identification of novel non-coding small RNAs from Streptococcus pneumoniae TIGR4 using high-resolution genome tiling arrays , 2010, BMC Genomics.

[79]  M. Winkler,et al.  Identification and Characterization of Noncoding Small RNAs in Streptococcus pneumoniae Serotype 2 Strain D 39 † , 2009 .

[80]  S. Brantl,et al.  The Transcriptional Repressor CcpN from Bacillus subtilis Uses Different Repression Mechanisms at Different Promoters* , 2009, The Journal of Biological Chemistry.

[81]  S. Arvidson,et al.  Activation of alpha‐toxin translation in Staphylococcus aureus by the trans‐encoded antisense RNA, RNAIII. , 1995, The EMBO journal.

[82]  Jeanette Treviño,et al.  A Genome-Wide Analysis of Small Regulatory RNAs in the Human Pathogen Group A Streptococcus , 2009, PloS one.

[83]  Suresh V. Chinni,et al.  Identification of differentially expressed small non-protein-coding RNAs in Staphylococcus aureus displaying both the normal and the small-colony variant phenotype , 2010, Journal of Molecular Medicine.

[84]  H. Malke,et al.  Dual Control of Streptokinase and Streptolysin S Production by the covRS and fasCAX Two-Component Regulators in Streptococcus dysgalactiae subsp. equisimilis , 2002, Infection and Immunity.

[85]  Jeanette Treviño,et al.  The group A Streptococcus small regulatory RNA FasX enhances streptokinase activity by increasing the stability of the ska mRNA transcript , 2010, Molecular microbiology.

[86]  B. Felden,et al.  A cis-antisense RNA acts in trans in Staphylococcus aureus to control translation of a human cytolytic peptide , 2011, Nature Structural &Molecular Biology.

[87]  I. Fierro-Monti,et al.  Differential expression of a Clostridium acetobutylicum antisense RNA: implications for regulation of glutamine synthetase , 1992, Journal of bacteriology.

[88]  Ulrike Mäder,et al.  A dual‐function sRNA from B. subtilis: SR1 acts as a peptide encoding mRNA on the gapA operon , 2010, Molecular microbiology.

[89]  T. Gingeras,et al.  Genome-wide antisense transcription drives mRNA processing in bacteria , 2011, Proceedings of the National Academy of Sciences.

[90]  RNA-Seq of Bacillus licheniformis: active regulatory RNA features expressed within a productive fermentation , 2013, BMC Genomics.

[91]  R. K. Gudipati,et al.  CodY Activates Transcription of a Small RNA in Bacillus subtilis , 2009, Journal of bacteriology.

[92]  E. Papoutsakis,et al.  Small RNAs in the Genus Clostridium , 2011, mBio.

[93]  David Hernández,et al.  Analysis of the Small RNA Transcriptional Response in Multidrug-Resistant Staphylococcus aureus after Antimicrobial Exposure , 2013, Antimicrobial Agents and Chemotherapy.

[94]  S. Brantl,et al.  BsrG/SR4 from Bacillus subtilis– the first temperature‐dependent type I toxin–antitoxin system , 2012, Molecular microbiology.

[95]  P. François,et al.  The importance of regulatory RNAs in Staphylococcus aureus. , 2014, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[96]  H. Hayashi,et al.  Clostridial VirR/VirS regulon involves a regulatory RNA molecule for expression of toxins , 2002, Molecular microbiology.

[97]  R. Novick,et al.  Inhibition of rot translation by RNAIII, a key feature of agr function , 2006, Molecular microbiology.

[98]  R. Brückner,et al.  Target evaluation of the non‐coding csRNAs reveals a link of the two‐component regulatory system CiaRH to competence control in Streptococcus pneumoniae R6 , 2013, Molecular microbiology.

[99]  Thomas R. Gingeras,et al.  An effort to make sense of antisense transcription in bacteria , 2012, RNA biology.

[100]  B. Felden,et al.  Functional and Structural Insights of a Staphylococcus aureus Apoptotic-like Membrane Peptide from a Toxin-Antitoxin Module* , 2012, The Journal of Biological Chemistry.

[101]  D. Gautheret,et al.  Experimental discovery of small RNAs in Staphylococcus aureus reveals a riboregulator of central metabolism , 2010, Nucleic acids research.

[102]  B. Schwikowski,et al.  Condition-Dependent Transcriptome Reveals High-Level Regulatory Architecture in Bacillus subtilis , 2012, Science.

[103]  T. Hartsch,et al.  Identification of novel growth phase- and media-dependent small non-coding RNAs in Streptococcus pyogenes M49 using intergenic tiling arrays , 2012, BMC Genomics.

[104]  Jessica M. Silvaggi,et al.  Richard Losick Bacillus subtilis Sporulation Control in Genes for Small , Noncoding RNAs under , 2005 .

[105]  P. Burguière,et al.  S-box and T-box riboswitches and antisense RNA control a sulfur metabolic operon of Clostridium acetobutylicum , 2008, Nucleic acids research.

[106]  Granger Ridout,et al.  Control of Virulence by Small RNAs in Streptococcus pneumoniae , 2012, PLoS pathogens.

[107]  Erik Aurell,et al.  A simple and efficient method to search for selected primary transcripts: non-coding and antisense RNAs in the human pathogen Enterococcus faecalis , 2011, Nucleic acids research.

[108]  T. Hartsch,et al.  The intracellular sRNA transcriptome of Listeria monocytogenes during growth in macrophages , 2011, Nucleic acids research.

[109]  Emanuel Barth,et al.  SR1—a small RNA with two remarkably conserved functions , 2012, Nucleic acids research.

[110]  G. Walker,et al.  A highly conserved protein of unknown function in Sinorhizobium meliloti affects sRNA regulation similar to Hfq , 2011, Nucleic acids research.

[111]  F. Vandenesch,et al.  Staphylococcus aureus RNAIII and the endoribonuclease III coordinately regulate spa gene expression , 2005, The EMBO journal.