Heidrich Nadja, Bauriedl Saskia, Barquist Lars, Li Lei, Schoen Christoph, Vogel Jörg
RNA Biology Group, Institute for Molecular Infection Biology (IMIB), University of Würzburg, D-97080 Würzburg, Germany.
Institute for Hygiene and Microbiology (IHM), University of Würzburg, D-97080 Würzburg, Germany.
Nucleic Acids Res. 2017 Jun 2;45(10):6147-6167. doi: 10.1093/nar/gkx168.
Neisseria meningitidis is a human commensal that can also cause life-threatening meningitis and septicemia. Despite growing evidence for RNA-based regulation in meningococci, their transcriptome structure and output of regulatory small RNAs (sRNAs) are incompletely understood. Using dRNA-seq, we have mapped at single-nucleotide resolution the primary transcriptome of N. meningitidis strain 8013. Annotation of 1625 transcriptional start sites defines transcription units for most protein-coding genes but also reveals a paucity of classical σ70-type promoters, suggesting the existence of activators that compensate for the lack of -35 consensus sequences in N. meningitidis. The transcriptome maps also reveal 65 candidate sRNAs, a third of which were validated by northern blot analysis. Immunoprecipitation with the RNA chaperone Hfq drafts an unexpectedly large post-transcriptional regulatory network in this organism, comprising 23 sRNAs and hundreds of potential mRNA targets. Based on this data, using a newly developed gfp reporter system we validate an Hfq-dependent mRNA repression of the putative colonization factor PrpB by the two trans-acting sRNAs RcoF1/2. Our genome-wide RNA compendium will allow for a better understanding of meningococcal transcriptome organization and riboregulation with implications for colonization of the human nasopharynx.
脑膜炎奈瑟菌是一种人类共生菌,也可引起危及生命的脑膜炎和败血症。尽管越来越多的证据表明脑膜炎奈瑟菌存在基于RNA的调控,但它们的转录组结构和调控小RNA(sRNA)的输出仍未完全了解。我们使用dRNA-seq技术,以单核苷酸分辨率绘制了脑膜炎奈瑟菌8013菌株的初级转录组图谱。对1625个转录起始位点的注释确定了大多数蛋白质编码基因的转录单元,但也揭示了经典σ70型启动子的缺乏,这表明存在补偿脑膜炎奈瑟菌中-35共有序列缺失的激活因子。转录组图谱还揭示了65个候选sRNA,其中三分之一通过Northern印迹分析得到验证。用RNA伴侣Hfq进行免疫沉淀在该生物体中勾勒出一个出乎意料的大的转录后调控网络,该网络由23个sRNA和数百个潜在的mRNA靶标组成。基于这些数据,我们使用新开发的gfp报告系统验证了两种反式作用sRNA RcoF1/2对假定的定植因子PrpB的Hfq依赖性mRNA抑制作用。我们的全基因组RNA汇编将有助于更好地理解脑膜炎奈瑟菌的转录组组织和核糖调控,这对人类鼻咽部的定植具有重要意义。