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BMC Genomics. 2015 May 30;16:419. doi: 10.1186/s12864-015-1583-4.

Single nucleotide resolution RNA-seq uncovers new regulatory mechanisms in the opportunistic pathogen Streptococcus agalactiae.

Author information

1
Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram Positif, 28 rue du Docteur Roux, 75724,, Paris Cedex 15, France. ichupin@pasteur.fr.
2
CNRS UMR 3525, Paris, France. ichupin@pasteur.fr.
3
Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram Positif, 28 rue du Docteur Roux, 75724,, Paris Cedex 15, France. esauvage@pasteur.fr.
4
CNRS UMR 3525, Paris, France. esauvage@pasteur.fr.
5
Institut Pasteur, Transcriptome and Epigenome Platform, 28 rue du Docteur Roux, 75724,, Paris Cedex 15, France. osisme@pasteur.fr.
6
Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram Positif, 28 rue du Docteur Roux, 75724,, Paris Cedex 15, France. avillain@pasteur.fr.
7
CNRS UMR 3525, Paris, France. avillain@pasteur.fr.
8
Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram Positif, 28 rue du Docteur Roux, 75724,, Paris Cedex 15, France. violette.da-cunha@pasteur.fr.
9
CNRS UMR 3525, Paris, France. violette.da-cunha@pasteur.fr.
10
Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram Positif, 28 rue du Docteur Roux, 75724,, Paris Cedex 15, France. marie-elise.caliot@pasteur.fr.
11
Institut Pasteur, Transcriptome and Epigenome Platform, 28 rue du Docteur Roux, 75724,, Paris Cedex 15, France. marie-agnes.dillies@pasteur.fr.
12
Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram Positif, 28 rue du Docteur Roux, 75724,, Paris Cedex 15, France. patrick.trieu-cuot@pasteur.fr.
13
Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, bâtiment 400, 91405, Orsay, France. philippe.bouloc@u-psud.fr.
14
Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, bâtiment 400, 91405, Orsay, France. marie-frederique.lartigue@univ-tours.fr.
15
Université de Tours, UMR1282 Infectiologie et Santé Publique, F-37000, Tours, France. marie-frederique.lartigue@univ-tours.fr.
16
CHRU de Tours, F-37044, Tours, France. marie-frederique.lartigue@univ-tours.fr.
17
INRA, UMR1282 Infectiologie et Santé Publique, F-37380, Nouzilly, France. marie-frederique.lartigue@univ-tours.fr.
18
Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram Positif, 28 rue du Docteur Roux, 75724,, Paris Cedex 15, France. philippe.glaser@pasteur.fr.
19
CNRS UMR 3525, Paris, France. philippe.glaser@pasteur.fr.

Abstract

BACKGROUND:

Streptococcus agalactiae, or Group B Streptococcus, is a leading cause of neonatal infections and an increasing cause of infections in adults with underlying diseases. In an effort to reconstruct the transcriptional networks involved in S. agalactiae physiology and pathogenesis, we performed an extensive and robust characterization of its transcriptome through a combination of differential RNA-sequencing in eight different growth conditions or genetic backgrounds and strand-specific RNA-sequencing.

RESULTS:

Our study identified 1,210 transcription start sites (TSSs) and 655 transcript ends as well as 39 riboswitches and cis-regulatory regions, 39 cis-antisense non-coding RNAs and 47 small RNAs potentially acting in trans. Among these putative regulatory RNAs, ten were differentially expressed in response to an acid stress and two riboswitches sensed directly or indirectly the pH modification. Strikingly, 15% of the TSSs identified were associated with the incorporation of pseudo-templated nucleotides, showing that reiterative transcription is a pervasive process in S. agalactiae. In particular, 40% of the TSSs upstream genes involved in nucleotide metabolism show reiterative transcription potentially regulating gene expression, as exemplified for pyrG and thyA encoding the CTP synthase and the thymidylate synthase respectively.

CONCLUSIONS:

This comprehensive map of the transcriptome at the single nucleotide resolution led to the discovery of new regulatory mechanisms in S. agalactiae. It also provides the basis for in depth analyses of transcriptional networks in S. agalactiae and of the regulatory role of reiterative transcription following variations of intra-cellular nucleotide pools.

PMID:
26024923
PMCID:
PMC4448216
DOI:
10.1186/s12864-015-1583-4
[Indexed for MEDLINE]
Free PMC Article

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