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RNA-binding protein Hfq downregulates locus of enterocyte effacement-encoded regulators independent of small regulatory RNA in enterohemorrhagic Escherichia coli
Molecular Microbiology ( IF 3.6 ) Pub Date : 2021-08-19 , DOI: 10.1111/mmi.14799
Naoki Sudo 1 , Kenichi Lee 1 , Yasuhiko Sekine 2 , Makoto Ohnishi 1 , Sunao Iyoda 1
Affiliation  

Enterohemorrhagic Escherichia coli (EHEC) causes severe human diseases worldwide. The type 3 secretion system and effector proteins are essential for EHEC infection, and are encoded by the locus of enterocyte effacement (LEE). RNA-binding protein Hfq is essential for small regulatory RNA (sRNA)-mediated regulation at a posttranscriptional level and full virulence of many pathogenic bacteria. Although two early studies indicated that Hfq represses LEE expression by posttranscriptionally controlling the expression of genes grlRA and/or ler, both of which encode LEE regulators mediating a positive regulatory loop, the detailed molecular mechanism and biological significance remain unclear. Herein, we show that LEE overexpression was caused by defective RNA-binding activity of the Hfq distal face, which posttranscriptionally represses grlA and ler expression. In vitro analyses revealed that the Hfq distal face directly binds near the translational initiation site of grlA and ler mRNAs, and inhibits their translation. Taken together, we conclude that Hfq inhibits grlA and ler translation by binding their mRNAs through the distal face in an sRNA-independent manner. Additionally, we show that Hfq-mediated repression of LEE is critical for normal EHEC growth because all suppressor mutations that restored the growth defect in the hfq mutant abolished hfq deletion-induced overexpression of LEE.

中文翻译:

RNA结合蛋白Hfq下调肠上皮细胞清除编码调节因子的位点,独立于肠出血性大肠杆菌中的小调节RNA

肠出血性大肠杆菌(EHEC)在全世界引起严重的人类疾病。3 型分泌系统和效应蛋白对 EHEC 感染至关重要,由肠上皮细胞清除 (LEE) 位点编码。RNA 结合蛋白 Hfq 对于转录后水平的小调节 RNA (sRNA) 介导的调节和许多病原菌的完全毒力至关重要。尽管两项早期研究表明 Hfq 通过转录后控制基因grlRA和/或ler的表达来抑制 LEE 表达,两者都编码介导正调节环的LEE调节因子,详细的分子机制和生物学意义仍不清楚。在这里,我们表明 LEE 过表达是由 Hfq 远端面的 RNA 结合活性缺陷引起的,它在转录后抑制grlAler表达。体外分析表明,Hfq 远端面直接结合grlAler mRNAs 的翻译起始位点附近,并抑制它们的翻译。总之,我们得出结论 Hfq 抑制grlAler通过以不依赖 sRNA 的方式通过远端面结合它们的 mRNA 进行翻译。此外,我们表明 Hfq 介导的 LEE 抑制对于正常 EHEC 生长至关重要,因为所有恢复 hfq 突变体中生长缺陷的抑制突变都消除了hfq缺失诱导的 LEE 过表达。
更新日期:2021-08-19
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