Genome-wide mapping of transcriptional start sites defines an extensive leaderless transcriptome in Mycobacterium tuberculosis.
Genome-wide mapping of transcriptional start sites defines an extensive leaderless transcriptome in Mycobacterium tuberculosis.
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DOI：
10.1016/j.celrep.2013.10.031
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发表时间：
2013-11-27
期刊：
影响因子：
8.8
通讯作者：
Young DB
中科院分区：
文献类型：
--
作者：
Cortes T;Schubert OT;Rose G;Arnvig KB;Comas I;Aebersold R;Young DB
破译介导结核分枝杆菌在复制和非复制状态之间转换的生理变化，对于了解病原体如何在单个宿主中持续数十年是至关重要的。我们将5‘端三磷酸富集库的RNA测序(RNA-seq)与常规RNA-seq相结合，以表征结核分枝杆菌启动子的结构和表达。我们确定了4000多个转录起始点(TSS)。值得注意的是，对于26%具有初级TSS的基因来说，转录起始点与注释的起始密码子重叠，产生缺少5‘UTR的无引导性转录本，因此，通常用于启动真细菌核糖体参与的Shine-Dalgarno序列。在饥饿的生长停滞模型中，编码具有活跃生长功能的蛋白质的基因明显从无领导转录组中消失，无领导mRNAs的总体表达显著增加。无领导基因的高比例在非复制型结核分枝杆菌的生理学中可能具有特别重要的作用。结核分枝杆菌体外活性启动子鉴定的资源结核分枝杆菌中所有基因的四分之一表达为无领导mRNAs无领导mRNAs与毒素-抗毒素模块差异相关在饥饿诱导的生长停滞期间，无领导mRNAs的丰度增加在这项研究中，Cortes，Young及其同事报告了在人类病原体结核分枝杆菌中转录起始点的全基因组图谱以及RNA测序和鸟枪式蛋白质组学。一个引人注目的发现是，有很高比例的基因以无前导转录本的形式表达，缺乏传统上翻译所需的Shine-Dalgarno序列。无领导转录本和Shine-Dalgarno转录本之间功能基因类别的分布表明，翻译特异性的变化可能在细菌感染期间的适应中发挥作用。
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. A resource for the identification of in vitro active promoters in M. tuberculosis A quarter of all genes in M. tuberculosis are expressed as leaderless mRNAs Leaderless mRNAs are differentially associated with toxin-antitoxin modules Abundance of leaderless mRNAs increases during starvation-induced growth arrest In this study, Cortes, Young, and colleagues report genome-wide mapping of transcriptional start sites combined with RNA sequencing and shotgun proteomics in the human pathogen Mycobacterium tuberculosis. A striking finding is a high proportion of genes expressed in the form of leaderless transcripts lacking the Shine-Dalgarno sequence conventionally required for translation. The distribution of functional gene classes between leaderless and Shine-Dalgarno transcriptomes suggests that changes in the specificity of translation may play a role in bacterial adaptation during infection.
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影响因子：
3.2
作者：
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通讯作者：
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DOI：
10.1074/mcp.m112.018846
发表时间：
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期刊：
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发表时间：
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影响因子：
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