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一种新型的电离辐射诱导的小 RNA,DrsS,可促进. 中活性氧的解毒。

A novel ionizing radiation-induced small RNA, DrsS, promotes the detoxification of reactive oxygen species in .

机构信息

RNA Biology Laboratory, Department of Chemistry, Indian Institute of Technology Delhi, New Delhi, India.

出版信息

Appl Environ Microbiol. 2024 May 21;90(5):e0153823. doi: 10.1128/aem.01538-23. Epub 2024 Apr 8.

Abstract

UNLABELLED

A plethora of gene regulatory mechanisms with eccentric attributes in confer it to possess a distinctive ability to survive under ionizing radiation. Among the many regulatory processes, small RNA (sRNA)-mediated regulation of gene expression is prevalent in bacteria but barely investigated in . In the current study, we identified a novel sRNA, DrsS, through RNA-seq analysis in cells while exposed to ionizing radiation. Initial sequence analysis for promoter identification revealed that is potentially co-transcribed with and from a single operon. Elimination of the allele in chromosome resulted in an impaired growth phenotype under γ-radiation. DrsS has also been found to be upregulated under oxidative and genotoxic stresses. Deletion of the gene resulted in the depletion of intracellular concentration of both Mn and Fe by ~70% and 40%, respectively, with a concomitant increase in carbonylation of intracellular protein. Complementation of gene in cells helped revert its intracellular Mn and Fe concentration and alleviated carbonylation of intracellular proteins. Cells with deleted gene exhibited higher sensitivity to oxidative stress than wild-type cells. Extrachromosomally expressed in cells retrieved its oxidative stress resistance properties by catalase-mediated detoxification of reactive oxygen species (ROS). binding assays indicated that DsrS directly interacts with the coding region of the transcript, thus possibly protecting it from cellular endonucleases . This study identified a novel small RNA DrsS and investigated its function under oxidative stress in .

IMPORTANCE

possesses an idiosyncratic quality to survive under extreme ionizing radiation and, thus, has evolved with diverse mechanisms which promote the mending of intracellular damages caused by ionizing radiation. As sRNAs play a pivotal role in modulating gene expression to adapt to altered conditions and have been delineated to participate in almost all physiological processes, understanding the regulatory mechanism of sRNAs will unearth many pathways that lead to radioresistance in . In that direction, DrsS has been identified to be a γ-radiation-induced sRNA, which is also induced by oxidative and genotoxic stresses. DrsS appeared to activate catalase under oxidative stress and detoxify intracellular ROS. This sRNA has also been shown to balance intracellular Mn(II) and Fe concentrations protecting intracellular proteins from carbonylation. This novel mechanism of DrsS identified in adds substantially to our knowledge of how this bacterium exploits sRNA for its survival under stresses.

摘要

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大量具有偏心属性的基因调控机制赋予了其在电离辐射下生存的独特能力。在许多调控过程中,细菌中普遍存在小 RNA(sRNA)介导的基因表达调控,但在 中几乎没有研究。在本研究中,我们通过电离辐射暴露时的细胞 RNA-seq 分析鉴定了一种新型 sRNA DrsS。启动子识别的初步序列分析表明,从单个操纵子上, 与 和 可能共转录。在 染色体中消除 等位基因导致 γ 辐射下生长表型受损。还发现 DrsS 在氧化和遗传毒性应激下上调。 基因缺失导致细胞内 Mn 和 Fe 浓度分别减少约 70%和 40%,同时细胞内蛋白质羰基化增加。在 细胞中补充 基因有助于恢复其细胞内 Mn 和 Fe 浓度并减轻细胞内蛋白质的羰基化。缺失 基因的细胞比野生型细胞对氧化应激更敏感。在 细胞中外源表达 可通过过氧化氢酶介导的活性氧(ROS)解毒来恢复其抗氧化应激特性。 结合测定表明,DsrS 直接与 转录本的编码区相互作用,从而可能保护其免受细胞内核酸内切酶的影响。这项研究鉴定了一种新型 sRNA DrsS,并研究了其在 氧化应激下的功能。

重要性

在极端电离辐射下具有独特的生存能力,因此进化出了多种促进修复由电离辐射引起的细胞内损伤的机制。由于 sRNA 在调节基因表达以适应变化的条件方面发挥着关键作用,并且已经被描述为参与几乎所有生理过程,因此了解 sRNA 的调控机制将揭示导致 的辐射抗性的许多途径。在这方面,已鉴定出 DrsS 是一种 γ 辐射诱导的 sRNA,也可被氧化和遗传毒性应激诱导。DrsS 似乎在氧化应激下激活过氧化氢酶并解毒细胞内的 ROS。还表明该 sRNA 可平衡细胞内 Mn(II)和 Fe 浓度,防止细胞内蛋白质发生碳化。在 中鉴定出的这种新型 DrsS 机制大大增加了我们对该细菌如何利用 sRNA 在应激下生存的认识。

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