Global intron retention mediated gene regulation during CD4+ T cell activation.
Global intron retention mediated gene regulation during CD4+ T cell activation.
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CD4( ) T 细胞激活过程中全局内含子保留介导的基因调控
DOI：
10.1093/nar/gkw591
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发表时间：
2016-08-19
影响因子：
14.9
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Ni T;Yang W;Han M;Zhang Y;Shen T;Nie H;Zhou Z;Dai Y;Yang Y;Liu P;Cui K;Zeng Z;Tian Y;Zhou B;Wei G;Zhao K;Peng W;Zhu J
T细胞活化是研究细胞对外源性刺激的反应的成熟模型。使用链特异性RNA-seq，我们观察到内含子保留在静息CD 4 + T细胞中的多聚腺苷酸化转录物中普遍存在，并且在T细胞活化后显著减少。一些证据表明，内含子保留的转录本比完全剪接的转录本更不稳定。引人注目的是，内含子保留（IR）水平的降低与稳态mRNA水平的增加相关。此外，大多数的基因上调活化的T细胞伴随着一个显着减少IR。这1583个基因中，185个基因主要是在IR水平调节，并高度富集在蛋白酶体途径，这是必要的适当的T细胞增殖和细胞因子释放。这些观察结果在人和小鼠CD 4 + T细胞中得到证实。我们的研究揭示了一种新的转录后调控机制，可能有助于协调和/或快速细胞反应的细胞外刺激，如急性感染。
T cell activation is a well-established model for studying cellular responses to exogenous stimulation. Using strand-specific RNA-seq, we observed that intron retention is prevalent in polyadenylated transcripts in resting CD4+ T cells and is significantly reduced upon T cell activation. Several lines of evidence suggest that intron-retained transcripts are less stable than fully spliced transcripts. Strikingly, the decrease in intron retention (IR) levels correlate with the increase in steady-state mRNA levels. Further, the majority of the genes upregulated in activated T cells are accompanied by a significant reduction in IR. Of these 1583 genes, 185 genes are predominantly regulated at the IR level, and highly enriched in the proteasome pathway, which is essential for proper T cell proliferation and cytokine release. These observations were corroborated in both human and mouse CD4+ T cells. Our study revealed a novel post-transcriptional regulatory mechanism that may potentially contribute to coordinated and/or quick cellular responses to extracellular stimuli such as an acute infection.
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影响因子：
10.5
作者：
Boutz PL;Bhutkar A;Sharp PA
通讯作者：
Sharp PA
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
7
作者：
Braunschweig U;Barbosa-Morais NL;Pan Q;Nachman EN;Alipanahi B;Gonatopoulos-Pournatzis T;Frey B;Irimia M;Blencowe BJ
通讯作者：
Blencowe BJ
影响因子：
7
作者：
Barski, Artem;Jothi, Raja;Zhao, Keji
通讯作者：
Zhao, Keji
影响因子：
4.5
作者：
Galante, PAF;Sakabe, NJ;De Souza, SJ
通讯作者：
De Souza, SJ