Nature 464, 250-255 (11 March 2010) | doi:10.1038/nature08756; Received 6 August 2009; Accepted 14 December 2009; Published online 17 February 2010
The primary transcriptome of the major human pathogen Helicobacter pylori
Cynthia M. Sharma1, Steve Hoffmann2, Fabien Darfeuille3,4, Jérémy Reignier3,4, Sven Findeiß2, Alexandra Sittka1, Sandrine Chabas3,4, Kristin Reiche5, Jörg Hackermüller5, Richard Reinhardt6, Peter F. Stadler2,5,7,8,9 & Jörg Vogel1,10
1. Max Planck Institute for Infection Biology, RNA Biology Group, D-10117 Berlin, Germany
2. University of Leipzig, Department of Computer Science & Interdisciplinary Centre for Bioinformatics, D-04107 Leipzig, Germany
3. INSERM U869 and,
4. Université de Bordeaux, F-33076 Bordeaux Cedex, France
5. Fraunhofer Institute for Cell Therapy and Immunology, RNomics Group, D-04103 Leipzig, Germany
6. Max Planck Institute for Molecular Genetics, D-14195 Berlin, Germany
7. Max Planck Institute for the Mathematics in Sciences, D-04103 Leipzig, Germany
8. University of Vienna, Institute for Theoretical Chemistry, A-1090 Vienna, Austria
9. The Santa Fe Institute, Santa Fe, 87501 New Mexico, USA
10. University of Würzburg, Institute for Molecular Infection Biology, D-97080 Würzburg, Germany
Correspondence to: Jörg Vogel1,10 Correspondence and requests for materials should be addressed to J.V. (Email: firstname.lastname@example.org).
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Genome sequencing of Helicobacter pylori has revealed the potential proteins and genetic diversity of this prevalent human pathogen, yet little is known about its transcriptional organization and noncoding RNA output. Massively parallel cDNA sequencing (RNA-seq) has been revolutionizing global transcriptomic analysis. Here, using a novel differential approach (dRNA-seq) selective for the 5′ end of primary transcripts, we present a genome-wide map of H. pylori transcriptional start sites and operons. We discovered hundreds of transcriptional start sites within operons, and opposite to annotated genes, indicating that complexity of gene expression from the small H. pylori genome is increased by uncoupling of polycistrons and by genome-wide antisense transcription. We also discovered an unexpected number of ~60 small RNAs including the ϵ-subdivision counterpart of the regulatory 6S RNA and associated RNA products, and potential regulators of cis- and trans-encoded target messenger RNAs. Our approach establishes a paradigm for mapping and annotating the primary transcriptomes of many living species.