Characterization of Chlamydial Rho and the Role of Rho-Mediated Transcriptional Polarity during Interferon Gamma-Mediated Tryptophan Limitation

Characterization of Chlamydial Rho and the Role of Rho-Mediated Transcriptional Polarity during Interferon Gamma-Mediated Tryptophan Limitation
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衣原体 Rho 的表征以及 Rho 介导的转录极性在干扰素 Gamma 介导的色氨酸限制过程中的作用

DOI:
10.1128/iai.00240-18
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发表时间:
2018
影响因子:
3.1
通讯作者:
Roy, Craig R.
Roy, Craig R.
中科院分区:
医学2区
文献类型:
--
作者:
Ouellette, Scot P.;Messerli, Parker R.;Wood, Nicholas A.;Hajovsky, Heather;Roy, Craig R.

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作为一种专性的细胞内,发育调节细菌,衣原体是敏感的氨基酸波动在其宿主细胞。当用细胞因子干扰素γ(IFN-γ)处理人类上皮细胞时,色氨酸(Trp)降解酶吲哚胺-2,3-双加氧酶被诱导。这些细胞内的衣原体缺乏色氨酸,并进入所谓的持久状态。衣原体缺乏许多真细菌对这种压力的严格反应。不寻常的是,衣原体的转录是全球性的升高,在色氨酸饥饿与转录的色氨酸密码子含有基因不成比例地增加。然而,Trp密码子的存在使操纵子或大基因中转录物的3′端不稳定。我们最初假设核糖体在Trp密码子上的停滞使得3′端对RNase活性敏感。因此,在未处理和IFN-γ处理的感染细胞中测量含有不同数量的Trp密码子的衣原体转录物的半衰期,以确定Trp密码子是否影响转录物的稳定性。然而,未检测到Trp密码子含量的影响。因此,我们研究了Rho依赖的转录终止是否可以在介导转录不稳定性中发挥作用。Rho作为一种中期基因产物表达,如预测的那样与自身相互作用,并且存在于所有衣原体物种中。通过Rho特异性抗生素双环霉素和Rho的过表达抑制Rho对衣原体是有害的。最后,当我们在双环霉素存在下测量Trp密码子3′的转录丰度时,我们观察到转录丰度增加。这些数据是第一个证明Rho在衣原体中的重要性和Rho依赖的转录极性在持久性过程中的作用。
As an obligate intracellular, developmentally regulated bacterium, Chlamydia is sensitive to amino acid fluctuations within its host cell. When human epithelial cells are treated with the cytokine interferon gamma (IFN-γ), the tryptophan (Trp)-degrading enzyme, indoleamine-2,3-dioxygenase, is induced. Chlamydiae within such cells are starved for Trp and enter a state of so-called persistence. Chlamydia lacks the stringent response used by many eubacteria to respond to this stress. Unusually, chlamydial transcription is globally elevated during Trp starvation with transcripts for Trp codon-containing genes disproportionately increased. Yet, the presence of Trp codons destabilized 3′ ends of transcripts in operons or large genes. We initially hypothesized that ribosome stalling on Trp codons rendered the 3′ ends sensitive to RNase activity. The half-life of chlamydial transcripts containing different numbers of Trp codons was thus measured in untreated and IFN-γ-treated infected cells to determine whether Trp codons influenced the stability of transcripts. However, no effect of Trp codon content was detected. Therefore, we investigated whether Rho-dependent transcription termination could play a role in mediating transcript instability. Rho is expressed as a midcycle gene product, interacts with itself as predicted, and is present in all chlamydial species. Inhibition of Rho via the Rho-specific antibiotic, bicyclomycin, and overexpression of Rho are detrimental to chlamydiae. Finally, when we measured transcript abundance 3′ to Trp codons in the presence of bicyclomycin, we observed that transcript abundance increased. These data are the first to demonstrate the importance of Rho in Chlamydia and the role of Rho-dependent transcription polarity during persistence.
DOI: 10.1126/science.282.5389.754
发表时间: 1998-10-23
期刊: SCIENCE
影响因子: 56.9
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期刊: The Journal of infectious diseases
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DOI: --
发表时间: 1995
影响因子: 3.9
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rho 来自极性抑制突变体的因子,其 RNA 相互作用存在缺陷。
DOI: --
发表时间: 1982
期刊: The Journal of biological chemistry
影响因子: --
作者:
Richardson,JP;Carey3rd,JL
通讯作者: Carey3rd,JL
DOI: 10.1093/infdis/138.5.655
发表时间: 1978
期刊: The Journal of infectious diseases
影响因子: --
作者:
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