Genome-wide Mapping of Transcriptional Start Sites Defines an Extensive Leaderless Transcriptome in Mycobacterium tuberculosis
Por:
Cortes T, Schubert OT, Rose G, Arnvig KB, Comas I, Aebersold R and Young DB
Publicada:
1 nov 2013
Categoría:
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Resumen:
Deciphering physiological changes that mediate transition of Mycobacterium tuberculosis between replicating and nonreplicating states is essential to understanding how the pathogen can persist in an individual host for decades. We have combined RNA sequencing (RNA-seq) of 50 triphosphate-enriched libraries with regular RNA-seq to characterize the architecture and expression of M. tuberculosis promoters. We identified over 4,000 transcriptional start sites (TSSs). Strikingly, for 26% of the genes with a primary TSS, the site of transcriptional initiation overlapped with the annotated start codon, generating leaderless transcripts lacking a 5' UTR and, hence, the Shine-Dalgarno sequence commonly used to initiate ribosomal engagement in eubacteria. Genes encoding proteins with active growth functions were markedly depleted from the leaderless transcriptome, and there was a significant increase in the overall representation of leaderless mRNAs in a starvation model of growth arrest. The high percentage of leaderless genes may have particular importance in the physiology of nonreplicating M. tuberculosis.
Filiaciones:
Cortes T:
Division of Mycobacterial Research, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
Schubert OT:
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland
Systems Biology Graduate School, 8057 Zurich, Switzerland
Rose G:
Division of Mycobacterial Research, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
Arnvig KB:
Division of Mycobacterial Research, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
Institute of Structural and Molecular Biology, University College London, London WC1E 6BT, UK
:
Genomics and Health Unit, Centre for Public Health Research (FISABIO-CSISP), 46020 Valencia, Spain
CIBER in Epidemiology and Public Health, 28029 Madrid, Spain
Aebersold R:
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland
Faculty of Science, University of Zurich, 8057 Zurich, Switzerland
Young DB:
Division of Mycobacterial Research, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UK
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