Global Analysis of the E. coli Toxin MazF Reveals Widespread Cleavage of mRNA and the Inhibition of rRNA Maturation and Ribosome Biogenesis.

Global Analysis of the E. coli Toxin MazF Reveals Widespread Cleavage of mRNA and the Inhibition of rRNA Maturation and Ribosome Biogenesis.
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DOI:
10.1016/j.molcel.2018.04.026
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发表时间:
2018-06-07
期刊:
影响因子:
16
通讯作者:
Laub MT
Laub MT
中科院分区:
生物学1区
文献类型:
--
作者:
Culviner PH;Laub MT

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毒素-抗毒素系统是广泛分布的遗传模块,调节细菌的生长和持久性。许多系统,包括E.大肠杆菌MazEF,包括作为核糖核酸内切酶的毒素,但这些毒素的全套靶标仍然不清楚。以前对有限的一组转录本的研究表明,MazF创建了一个无前导mRNA库,这些mRNA优先由MazF切割成熟16 S rRNA创建的专门核糖体翻译。在这里,使用配对末端RNA-Seq和核糖体分析,我们提供了MazF切割特异性及其靶点的全面,全局分析。我们发现MazF在其编码区的多个位点切割大多数转录物,只有很少的全长无前导mRNA。此外,我们的研究结果表明,MazF不会产生大量专门的核糖体,而是通过靶向核糖体蛋白转录物和rRNA前体快速破坏核糖体生物合成,帮助抑制细胞生长。
Toxin-antitoxin systems are widely distributed genetic modules that regulate growth and persistence in bacteria. Many systems, including E. coli MazEF, include toxins that are endoribonucleases, but the full set of targets for these toxins remains poorly defined. Previous studies on a limited set of transcripts suggested that MazF creates a pool of leaderless mRNAs that are preferentially translated by specialized ribosomes created through MazF cleavage of mature 16S rRNA. Here, using paired-end RNA-Seq and ribosome profiling, we provide a comprehensive, global analysis of MazF cleavage specificity and its targets. We find that MazF cleaves most transcripts at multiple sites within their coding regions, with very few full-length, leaderless mRNAs created. Additionally, our results demonstrate that MazF does not create a large pool of specialized ribosomes, but instead rapidly disrupts ribosome biogenesis by targeting both ribosomal protein transcripts and rRNA precursors, helping to inhibit cell growth.
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