Global analysis of alternative splicing during T-cell activation
Global analysis of alternative splicing during T-cell activation
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DOI：
10.1261/rna.457207
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发表时间：
2007-04-01
期刊：
影响因子：
4.5
通讯作者：
Lynch, Kristen W.
中科院分区：
文献类型：
--
作者：
Ip, Joanna Y.;Tong, Alan;Lynch, Kristen W.
人们对选择性剪接（AS）在引发免疫反应中的作用知之甚少。我们使用定量 AS 微阵列分析来调查 Jurkat 细胞（一种白血病衍生的 T 细胞系）激活期间 AS 的变化。我们的结果表明，大约 10%-15% 的分析替代外显子在激活过程中包含水平发生 > 10% 的变化。大多数显示差异 AS 水平的基因与显示差异转录物水平的基因组不同。这两个基因组也具有重叠但又不同的功能作用。例如，在 T 细胞激活过程中表现出差异 AS 模式的基因通常与细胞周期调节密切相关，而具有差异转录水平的基因在与免疫防御和细胞骨架结构更直接相关的功能上高度丰富。在 T 细胞激活中起重要作用的基因中检测到了先前未知的 AS 事件，并且在正常人外周 CD4+ 和 CD8+ 淋巴细胞的激活过程中也观察到了这些 AS 水平的变化。总之，通过使用 AS 微阵列分析，我们发现了许多与 T 细胞激活相关的新 AS 变化。我们的结果表明 AS 在哺乳动物免疫反应的调节中发挥着广泛的作用。
The role of alternative splicing (AS) in eliciting immune responses is poorly understood. We used quantitative AS microarray profiling to survey changes in AS during activation of Jurkat cells, a leukemia-derived T-cell line. Our results indicate that similar to 10%-15% of the profiled alternative exons undergo a > 10% change in inclusion level during activation. The majority of the genes displaying differential AS levels are distinct from the set of genes displaying differential transcript levels. These two gene sets also have overlapping yet distinct functional roles. For example, genes that show differential AS patterns during T-cell activation are often closely associated with cell-cycle regulation, whereas genes with differential transcript levels are highly enriched in functions associated more directly with immune defense and cytoskeletal architecture. Previously unknown AS events were detected in genes that have important roles in T-cell activation, and these AS level changes were also observed during the activation of normal human peripheral CD4+ and CD8+ lymphocytes. In summary, by using AS microarray profiling, we have discovered many new AS changes associated with T-cell activation. Our results suggest an extensive role for AS in the regulation of the mammalian immune response.