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An in silico model for identification of small RNAs in whole bacterial genomes: characterization of antisense RNAs in pathogenic Escherichia coli and Streptococcus agalactiae strains

By Christophe Pichon, Laurence du Merle, Marie Elise Caliot, Patrick Trieu-Cuot and Chantal Le Bouguénec


Characterization of small non-coding ribonucleic acids (sRNA) among the large volume of data generated by high-throughput RNA-seq or tiling microarray analyses remains a challenge. Thus, there is still a need for accurate in silico prediction methods to identify sRNAs within a given bacterial species. After years of effort, dedicated software were developed based on comparative genomic analyses or mathematical/statistical models. Although these genomic analyses enabled sRNAs in intergenic regions to be efficiently identified, they all failed to predict antisense sRNA genes (asRNA), i.e. RNA genes located on the DNA strand complementary to that which encodes the protein. The statistical models enabled any genomic region to be analyzed theorically but not efficiently. We present a new model for in silico identification of sRNA and asRNA candidates within an entire bacterial genome. This model was successfully used to analyze the Gram-negative Escherichia coli and Gram-positive Streptococcus agalactiae. In both bacteria, numerous asRNAs are transcribed from the complementary strand of genes located in pathogenicity islands, strongly suggesting that these asRNAs are regulators of the virulence expression. In particular, we characterized an asRNA that acted as an enhancer-like regulator of the type 1 fimbriae production involved in the virulence of extra-intestinal pathogenic E. coli

Topics: Computational Biology
Publisher: Oxford University Press
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    1. (2002). A bioinformatics based approach to discover small RNA genes in the Escherichia coli genome.
    2. (2001). A computational approach to identify genes for functional RNAs in genomic sequences.
    3. (2009). A genome-wide analysis of small regulatory RNAs in the human pathogen group A Streptococcus.
    4. (1991). A novel RNA product of the tyrT operon of Escherichia coli.
    5. (2000). A rapid method for efficient gene replacement in the filamentous fungus Aspergillus nidulans.
    6. (2009). A search for small noncoding RNAs in Staphylococcus aureus reveals a conserved sequence motif for regulation.
    7. (2005). A small bacterial RNA regulates a putative ABC transporter.
    8. (2007). A small non-coding RNA of the invasion gene island (SPI-1) represses outer membrane protein synthesis from the Salmonella core genome.
    9. (1995). A small RNA acts as an antisilencer of the H-NS-silenced rcsA gene of Escherichia coli.
    10. (1982). A small RNA that complements mutants in the RNA processing enzyme ribonuclease P.
    11. (2010). A Staphylococcus aureus small RNA is required for bacterial virulence and regulates the expression of an immune-evasion molecule.
    12. (1984). A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA).
    13. (2007). An antisense RNA controls synthesis of an SOS-induced toxin evolved from an antitoxin.
    14. (2010). An antisense RNA that governs the expression kinetics of a multifunctional virulence gene.
    15. (2008). An internal antisense RNA regulates expression of the photosynthesis gene isiA.
    16. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method.
    17. (2010). Bacterial antisense RNAs: how many are there, and what are they doing?
    18. (2001). Biofilm formation in a hydrodynamic environment by novel fimH variants and ramifications for virulence.
    19. (2010). Cartography of methicillin-resistant S. aureus transcripts: detection, orientation and temporal expression during growth phase and stress conditions.
    20. (1982). Cloning of the chromosomal determinants encoding haemolysin production and mannose resistant haemagglutination in Escherichia coli.
    21. (2001). Computational identification of noncoding RNAs in E. coli by comparative genomics.
    22. (2006). Demonstration of regulatory cross-talk between P fimbriae and type 1 fimbriae in uropathogenic Escherichia coli.
    23. (2005). Detection of 50- and 30-UTR-derived small RNAs and cis-encoded antisense RNAs in Escherichia coli.
    24. (2006). Detection of non-coding RNAs on the basis of predicted secondary structure formation free energy change.
    25. (2007). Development of intracellular bacterial communities of uropathogenic Escherichia coli depends on type 1 pili.
    26. (1988). DNA polymerase I activity in Escherichia coli is influenced by spot 42 RNA.
    27. (2006). Down-regulation of porins by a small RNA bypasses the essentiality of the RIP protease RseP in Escherichia coli.
    28. (2001). Emerging views on tmRNA-mediated protein tagging and ribosome rescue.
    29. (2005). Envelope stress responses and Gram-negative bacterial pathogenesis.
    30. (1999). Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure.
    31. (2010). Experimental discovery of small RNAs in Staphylococcus aureus reveals a riboregulator of central metabolism.
    32. (2010). Experimental identification and characterization of 97 novel npcRNA candidates in Salmonella enterica serovar Typhi.
    33. (2000). fhlA repression by OxyS RNA: kissing complex formation at two sites results in a stable antisense-target RNA complex.
    34. (2000). Flexible sequence similarity searching with the FASTA3 program package.
    35. (1995). Gene disruption in Escherichia coli: TcR and KmR cassette with the option of Flp-catalyzed excision of the antibiotic resistance determinant.
    36. (1998). Genetic analysis of Escherichia coli biofilm formation: roles of flagella, motility, chemotaxis and type 1 pili.
    37. (2002). Genome sequence of Streptococcus agalactiae, a pathogen causing invasive neonatal disease.
    38. (2011). Genome-wide detection of novel regulatory RNAs
    39. Genome-wide identification of transcription start sites, promoters and transcription factor binding sites in E.
    40. (2010). Genomix SELEX for Hfq binding RNAs identifies genomic aptamers predominantly in antisense transcripts.
    41. (2003). Global analysis of small RNA and mRNA targets of Hfq.
    42. (2005). Global epithelial cell transcriptional responses reveal Streptococcus pyogenes Fas regulator activity association with bacterial aggressiveness.
    43. (2005). Identification of cyanobacterial non-coding RNAs by comparative genome analysis.
    44. (2010). Identification of differentially expressed small non-protein-coding RNAs in Staphylococcus aureus displaying both the normal and the small-colony variant phenotype.
    45. (2010). Identification of genes for small non-coding RNAs that belongs to the regulon of the two component regulatory system CiaRH in Streptococcus.
    46. (2006). Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli: a comparative genomics approach.
    47. (2000). Identification of group B streptococcal Sip protein, which elicits cross protective immunity.
    48. (2001). Identification of novel small RNAs using comparative genomics and microarrays.
    49. (2007). 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.
    50. (2008). Impact of the RNA chaperone Hfq on the fitness and virulence potential of uropathogenic Escherichia coli.
    51. (1999). Improved microbial gene identification with GLIMMER.
    52. (1997). Independent and tight regulation of transcriptional units in Escherichia coli via the LacR/O, The TetR/O and AraC/I1-I2 regulatory elements.
    53. (2003). Intergenic Sequence Inspector: searching and identifying bacterial RNAs.
    54. (2008). Invasive group B streptococcal infections in infants,
    55. (1986). Mechanism for the autogenous control of the crp operon: Transcriptional inhibition by a divergent RNA transcript.
    56. (2001). MELTING, computing the melting temperature of nucleic acid duplex.
    57. (2002). Molecular characterization of long direct repeat (LDR) sequences expressing a stable mRNA encoding for a 35-amino-acid cell-killing peptide and a cis-encoded small antisense RNA in Escherichia coli.
    58. (2001). Noncoding RNA gene detection using comparative sequence analysis.
    59. (2001). Novel small RNA-encoding genes in the intergenic regions of Escherichia coli.
    60. (2000). One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products.
    61. (2009). Organised genome dynamics in the Escherichia coli species: the path to adaptation. PLoS
    62. (2004). Pathogenic Escherichia coli.
    63. (2005). Predicting non-coding RNA genes in Escherichia coli with boosted genetic programming.
    64. (2006). Prediction of non-coding and antisense RNA genes in Escherichia coli with Gapped Markov Model.
    65. (2001). Prediction of rho-independent transcriptional terminators in Escherichia coli.
    66. (2007). Proteins that interact with bacterial small RNA regulators.
    67. (2006). PSoL: a positive sample only learning algorithm for finding non-coding RNA genes.
    68. (2007). Rapid, accurate, computational discovery of Rho-independent transcription terminators illuminates their relationship to DNA uptake.
    69. (2001). Regulation of RpoS by a novel small RNA: the characterization of RprA.
    70. (1992). Regulation of the expression of the cell cycle gene ftsZ by DicF antisense RNA. Division does not require a fixed number of FtsZ molecules.
    71. (2007). Regulatory mechanisms employed by cis-encoded antisense RNAs.
    72. (2009). Regulatory RNAs in Bacteria.
    73. (2001). RNAMotif, an RNA secondary structure definition and search algorithm.
    74. (2003). RNomics in Escherichia coli detects new sRNA species and indicates parallel transcriptional output in bacteria.
    75. (1996). Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA.
    76. (2006). Role of pathogenicity island-associated integrases in the genome plasticity of uropathogenic Escherichia coli strain 536.
    77. (2002). Searching for RNA genes using base composition statistics.
    78. (1971). Sequence of 6S
    79. (2009). Single-pass classification of all non-coding sequences in a bacterial genome using phylogenetic profiles.
    80. (2005). Small RNA genes expressed from Staphylococcus aureus genomic and pathogenicity islands with specific expression among pathogenic strains.
    81. (2008). Small RNA genes identifications and mRNA targets predictions in Bacteria.
    82. (2010). Small RNAs promote mRNA stability to activate the synthesis of virulence factors.
    83. (1993). Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule.
    84. (1984). The 4.5 S RNA gene of Escherichia coli is essential for cell growth.
    85. (2001). The afa-8 gene cluster is carried by a pathogenicity island inserted into the tRNAPhe of human and bovine pathogenic Escherichia coli isolates.
    86. (2000). The gcvB gene encodes a small untranslated RNA involved in expression of the dipeptide and oligopeptide transport systems in Escherichia coli.
    87. (2009). The Listeria transcriptional landscape from saprophytism to virulence.
    88. (2010). The primary transcriptome of the major human pathogen Helicobacter pylori.
    89. (1997). The RNA molecule CsrB binds to the global regulatory protein CsrA and antagonizes its activity in Escherichia coli.
    90. (2006). The role of RNAs in the regulation of virulence-gene expression.
    91. (2004). The Small RNA IstR Inhibits Synthesis of an SOS-Induced Toxic Peptide.
    92. (1989). Transcription of the sulA-ompA region of Escherichia coli during the SOS response and the role of an antisense RNA molecule.
    93. (2002). Transcriptome analysis of Escherichia coli using high-density oligonucleotide probe arrays.
    94. (2007). Translational control and target recognition by Escherichia coli small RNAs in vivo.
    95. (2009). Uropathogenic Escherichia coli AL511 requires flagellum to enter renal collecting duct cells.

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