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Crucial Role of the C-Terminal Domain of Hfq Protein in Genomic Instability
Microorganisms ( IF 4.5 ) Pub Date : 2020-10-17 , DOI: 10.3390/microorganisms8101598
Virali J. Parekh , Frank Wien , Wilfried Grange , Thomas A. De Long , Véronique Arluison , Richard R. Sinden

G-rich DNA repeats that can form G-quadruplex structures are prevalent in bacterial genomes and are frequently associated with regulatory regions of genes involved in virulence, antigenic variation, and antibiotic resistance. These sequences are also inherently mutagenic and can lead to changes affecting cell survival and adaptation. Transcription of the G-quadruplex-forming repeat (G3T)n in E. coli, when mRNA comprised the G-rich strand, promotes G-quadruplex formation in DNA and increases rates of deletion of G-quadruplex-forming sequences. The genomic instability of G-quadruplex repeats may be a source of genetic variability that can influence alterations and evolution of bacteria. The DNA chaperone Hfq is involved in the genetic instability of these G-quadruplex sequences. Inactivation of the hfq gene decreases the genetic instability of G-quadruplex, demonstrating that the genomic instability of this regulatory element can be influenced by the E. coli highly pleiotropic Hfq protein, which is involved in small noncoding RNA regulation pathways, and DNA organization and packaging. We have shown previously that the protein binds to and stabilizes these sequences, increasing rates of their genomic instability. Here, we extend this analysis to characterize the role of the C-terminal domain of Hfq protein in interaction with G-quadruplex structures. This allows to better understand the function of this specific region of the Hfq protein in genomic instability.

中文翻译:

Hfq蛋白C末端结构域在基因组不稳定中的关键作用

可以形成G-四链体结构的富含G的DNA重复序列在细菌基因组中很普遍,并且经常与涉及毒力,抗原变异和抗生素抗性的基因的调控区域相关。这些序列也具有固有的诱变性,并可导致影响细胞存活和适应的变化。在大肠杆菌中转录G-四链体形成重复(G 3 T)n,当mRNA包含富含G的链时,可促进DNA中G-四链体的形成并增加G-四链体形成序列的缺失率。G-四链体重复序列的基因组不稳定性可能是遗传变异的来源,可能影响细菌的改变和进化。DNA伴侣Hfq与这些G-四链体序列的遗传不稳定性有关。hfq基因的失活减少了G-四体的遗传不稳定性,表明该调控元件的基因组不稳定性可能受到大肠杆菌的影响高度多效性的Hfq蛋白,参与小的非编码RNA调节途径以及DNA的组织和包装。先前我们已经表明,蛋白质结合并稳定了这些序列,从而增加了其基因组不稳定性的速率。在这里,我们扩展此分析以表征Hfq蛋白的C末端结构域在与G-四链体结构相互作用中的作用。这可以更好地了解Hfq蛋白这一特定区域在基因组不稳定中的功能。
更新日期:2020-10-17
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