bacterial infection drives the expression dynamics of microRNAs and their isomiRs.
bacterial infection drives the expression dynamics of microRNAs and their isomiRs.
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DOI：
10.1371/journal.pgen.1005064
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发表时间：
2015-03
期刊：
影响因子：
4.5
通讯作者：
Quintana-Murci L
中科院分区：
文献类型：
--
作者：
Siddle KJ;Tailleux L;Deschamps M;Loh YH;Deluen C;Gicquel B;Antoniewski C;Barreiro LB;Farinelli L;Quintana-Murci L
宿主细胞对感染的转录反应的最佳协调对于建立适当的免疫结果是必不可少的。在这种情况下，microRNA（miRNAs）-基因表达的重要表观遗传调节因子-在调节哺乳动物免疫系统中的作用越来越受到认可。然而，miRNA及其亚型在感染应答中的表达动力学在很大程度上仍未被探索。在这里，我们的特点是人类树突状细胞的全基因组的miRNA转录反应，随着时间的推移，各种分枝杆菌不同的毒力，以及其他细菌以外的属分枝杆菌，使用小RNA测序。我们检测到存在一个核心的时间响应感染，跨细菌共享，包括49个miRNAs，突出了一组miRNAs，可能在调节基本的细胞应激反应中发挥重要作用。尽管有这样广泛共享的表达动力学，我们确定了miRNA对细菌感染反应的特异性变异元素，包括miR-132/212家族对分枝杆菌感染反应的毒力依赖性诱导。我们还发现感染对miRNA发夹臂的相对丰度和miRNA亚型的表达动力学都有很大影响。我们观察到相对臂表达和isomiR在细菌中分布的广泛一致的变化表明，miRNA应答中的这种额外的内部变异层代表了感染后微小miRNA介导的调节的额外来源。总的来说，这项研究增加了我们对miRNAs响应细菌感染的动力学和作用的理解，揭示了其内部变异的新特征，并确定了可能导致分枝杆菌感染致病性差异的候选miRNAs。microRNA（miRNAs）是一类小的非编码RNA，通过抑制靶基因的表达来调节重要的细胞过程。近年来，已经清楚的是，miRNA在对感染的免疫应答的调节中发挥关键作用，感染是一种高度复杂的表型，涉及通用和感染特异性应答的激活。然而，目前还不清楚miRNAs在多大程度上参与了这两种反应的调节。在这里，专注于miRNA对分枝杆菌的反应，主要的公共卫生重要性的病原体，我们提出了第一个比较，基于深度测序的miRNA对一组细菌感染的反应分析。我们定义了一组在基本细胞应激反应中起重要作用的miRNA，并确定了病原体特异性miRNA反应，这些反应反映了某些病原体干扰宿主对感染反应的机制。此外，我们发现感染可以改变miRNA亚型的表达水平和比例，这些亚型是来自相同miRNA的转录本，但它们的核苷酸序列略有不同。这项研究突出了感染后miRNA表达动力学的一个新方面，并增加了我们对参与宿主细胞感染反应的miRNA介导机制的理解。
The optimal coordination of the transcriptional response of host cells to infection is essential for establishing appropriate immunological outcomes. In this context, the role of microRNAs (miRNAs) – important epigenetic regulators of gene expression – in regulating mammalian immune systems is increasingly well recognised. However, the expression dynamics of miRNAs, and that of their isoforms, in response to infection remains largely unexplored. Here, we characterized the genome-wide miRNA transcriptional responses of human dendritic cells, over time, to various mycobacteria differing in their virulence as well as to other bacteria outside the genus Mycobacterium, using small RNA-sequencing. We detected the presence of a core temporal response to infection, shared across bacteria, comprising 49 miRNAs, highlighting a set of miRNAs that may play an essential role in the regulation of basic cellular responses to stress. Despite such broadly shared expression dynamics, we identified specific elements of variation in the miRNA response to infection across bacteria, including a virulence-dependent induction of the miR-132/212 family in response to mycobacterial infections. We also found that infection has a strong impact on both the relative abundance of the miRNA hairpin arms and the expression dynamics of miRNA isoforms. That we observed broadly consistent changes in relative arm expression and isomiR distribution across bacteria suggests that this additional, internal layer of variability in miRNA responses represents an additional source of subtle miRNA-mediated regulation upon infection. Collectively, this study increases our understanding of the dynamism and role of miRNAs in response to bacterial infection, revealing novel features of their internal variability and identifying candidate miRNAs that may contribute to differences in the pathogenicity of mycobacterial infections. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate important cellular processes by inhibiting the expression of gene targets. In recent years, it has become clear that miRNAs play a critical role in the regulation of the immune response to infection, a highly complex phenotype involving the activation of both generic and infection-specific responses. However, it remains unclear to what extent miRNAs are involved in the regulation of these two types of response. Here, focusing on the miRNA response to mycobacteria, pathogens of major public health importance, we present the first comparative, deep sequencing-based analysis of the miRNA response to a panel of bacterial infections. We define a set of miRNAs that play an essential role in basic cellular responses to stress and identify pathogen-specific miRNA responses that reflect mechanisms by which certain pathogens interfere with the host response to infection. In addition, we show that infection can alter the expression level and proportions of miRNA isoforms, transcripts originating from the same miRNA but with slight differences in their nucleotide sequences. This study highlights a novel aspect of miRNA expression dynamics upon infection and increases our understanding of miRNA-mediated mechanisms involved in host cellular responses to infection.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1126/science.1179050
发表时间：
2009-10-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Amit I;Garber M;Chevrier N;Leite AP;Donner Y;Eisenhaure T;Guttman M;Grenier JK;Li W;Zuk O;Schubert LA;Birditt B;Shay T;Goren A;Zhang X;Smith Z;Deering R;McDonald RC;Cabili M;Bernstein BE;Rinn JL;Meissner A;Root DE;Hacohen N;Regev A
通讯作者：
Regev A
影响因子：
64.5
作者：
Chevrier N;Mertins P;Artyomov MN;Shalek AK;Iannacone M;Ciaccio MF;Gat-Viks I;Tonti E;DeGrace MM;Clauser KR;Garber M;Eisenhaure TM;Yosef N;Robinson J;Sutton A;Andersen MS;Root DE;von Andrian U;Jones RB;Park H;Carr SA;Regev A;Amit I;Hacohen N
通讯作者：
Hacohen N
影响因子：
2.2
作者：
Fournier, David A.;Skaug, Hans J.;Sibert, John
通讯作者：
Sibert, John
DOI：
10.1073/pnas.1115761109
发表时间：
2012-01-24
影响因子：
11.1
作者：
Barreiro, Luis B.;Tailleux, Ludovic;Gilad, Yoav
通讯作者：
Gilad, Yoav