miRNA profiling of naïve, effector and memory CD8 T cells.
miRNA profiling of naïve, effector and memory CD8 T cells.
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幼稚，效应子和记忆CD8 T细胞的miRNA分析。
DOI：
10.1371/journal.pone.0001020
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发表时间：
2007-10-10
期刊：
影响因子：
3.7
通讯作者：
Manjunath, N.
中科院分区：
文献类型：
--
作者：
Wu, Haoquan;Neilson, Joel R.;Kumar, Priti;Manocha, Monika;Shankar, Premlata;Sharp, Phillip A.;Manjunath, N.
microRNA 最近已成为发育和细胞分化过程中基因表达的主要调节因子。尽管抗原诱导的 T 细胞分化过程中也会发生基因表达的深刻变化，但 miRNA 在此过程中的作用尚不清楚。我们使用 3 种不同的方法（小 RNA 克隆、miRNA 微阵列分析和实时 PCR）比较了抗原特异性初始、效应和记忆 CD8+ T 细胞之间的 miRNA 表达谱。尽管许多 miRNA 在所有 T 细胞亚群中都有表达，但仅 7 个 miRNA（miR-16、miR-21、miR-142-3p、miR-142-5p、miR-150、miR-15b 和 let-7f）的频率就占所有 miRNA 的~60%，并且它们的表达量比其他表达的 miRNA 高数倍。与初始细胞相比，在效应 T 细胞中观察到 miRNA（包括 6/7 显性表达的 miRNA）的整体下调，并且 miRNA 表达水平往往在记忆 T 细胞中恢复。然而，与初始 T 细胞相比，效应 T 细胞和记忆 T 细胞中的一些 miRNA，尤其是 miR-21 含量更高。这些结果表明，伴随着基因表达的深刻变化，miRNA 谱也在 T 细胞分化过程中动态变化。克隆的成熟 miRNA 的序列分析揭示了广泛的末端多态性。虽然 3' 端多态性占主导地位，但两端的异质性，在 miR-142 中也观察到类似 drosha/dicer 加工转移，这表明可能存在一种产生新 miRNA 和/或使 miRNA 靶标选择多样化的新机制。总的来说，我们的结果表明 miRNA 表达的动态变化可能对于抗原诱导 T 细胞分化过程中基因表达的调节很重要。我们的研究还提出了 miRNA 生物发生和功能的可能新机制。
microRNAs have recently emerged as master regulators of gene expression during development and cell differentiation. Although profound changes in gene expression also occur during antigen-induced T cell differentiation, the role of miRNAs in the process is not known. We compared the miRNA expression profiles between antigen-specific naïve, effector and memory CD8+ T cells using 3 different methods-small RNA cloning, miRNA microarray analysis and real-time PCR. Although many miRNAs were expressed in all the T cell subsets, the frequency of 7 miRNAs (miR-16, miR-21, miR-142-3p, miR-142-5p, miR-150, miR-15b and let-7f) alone accounted for ∼60% of all miRNAs, and their expression was several fold higher than the other expressed miRNAs. Global downregulation of miRNAs (including 6/7 dominantly expressed miRNAs) was observed in effector T cells compared to naïve cells and the miRNA expression levels tended to come back up in memory T cells. However, a few miRNAs, notably miR-21 were higher in effector and memory T cells compared to naïve T cells. These results suggest that concomitant with profound changes in gene expression, miRNA profile also changes dynamically during T cell differentiation. Sequence analysis of the cloned mature miRNAs revealed an extensive degree of end polymorphism. While 3′end polymorphisms dominated, heterogeneity at both ends, resembling drosha/dicer processing shift was also seen in miR-142, suggesting a possible novel mechanism to generate new miRNA and/or to diversify miRNA target selection. Overall, our results suggest that dynamic changes in the expression of miRNAs may be important for the regulation of gene expression during antigen-induced T cell differentiation. Our study also suggests possible novel mechanisms for miRNA biogenesis and function.
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影响因子：
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Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
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