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Cell Press, Cell Reports, 2(6), p. 415, 2014

DOI: 10.1016/j.celrep.2014.01.004

Cell Press, Cell Reports, 4(5), p. 1121-1131, 2013

DOI: 10.1016/j.celrep.2013.10.031

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Genome-wide Mapping of Transcriptional Start Sites Defines an Extensive Leaderless Transcriptome in Mycobacterium tuberculosis

Journal article published in 2013 by Teresa Cortes ORCID, Olga T. Schubert, Graham Rose, Kristine B. Arnvig ORCID, Iñaki Comas, Ruedi Aebersold, Douglas B. Young
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

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 5′ 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.