HuA and tristetraprolin are induced following T cell activation and display distinct but overlapping RNA binding specificities
HuA and tristetraprolin are induced following T cell activation and display distinct but overlapping RNA binding specificities
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DOI：
10.1074/jbc.m109511200
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发表时间：
2001-12-21
影响因子：
4.8
通讯作者：
Bohjanen, PR
中科院分区：
文献类型：
--
作者：
Raghavan, A;Robison, RL;Bohjanen, PR
在细胞因子和原癌基因转录物的 3'-非翻译区中发现的富含 AU 的元件调节 mRNA 降解，并作为 mRNA 稳定蛋白 HuA 和 mRNA 不稳定蛋白 tristetraprolin 的结合位点发挥作用。进行实验以评估纯化的人 T 淋巴细胞中 HuA 和 tristetraprolin 的表达，并评估这些蛋白质识别富含 AU 的特定序列的能力。 HuA 主要是一种核蛋白，也可以在静息 T 淋巴细胞的细胞质中找到。用抗T细胞受体抗体或佛波醇肉豆蔻酸酯乙酸酯和离子霉素的组合刺激T淋巴细胞后1小时内，观察到细胞质HuA RNA结合活性的增加。尽管在静息细胞中不存在，但在激活后 3-6 小时检测到细胞质三四脯氨酸蛋白。 HuA 识别 c-jun 或 c-myc mRNA 中发现的富含 AU 的特定序列，而三四脯氨酸很难识别这些序列。相比之下，tristetraprolin 可识别 IL-2 mRNA 中富含 AU 的序列，而 HuA 则很难识别该序列。然而，HuA 和 tristetraprolin 都识别来自 ic-fos、白介素-3、肿瘤坏死因子-α 和粒细胞/巨噬细胞集落刺激因子 mRNA 的富含 AU 的序列。 HuA 可能会在 T 淋巴细胞激活后暂时稳定富含 AU 元素的转录物子集，而 tristetraprolin 可能随后介导它们的降解。
AU-rich elements found in the 3 ' -untranslated regions of cytokine and proto-oncogene transcripts regulate mRNA degradation and function as binding sites for the mRNA-stabilizing protein HuA and the mRNA-destabilizing protein tristetraprolin. Experiments were performed to evaluate the expression of HuA and tristetraprolin in purified human T lymphocytes and to evaluate the ability of these proteins to recognize specific AU-rich sequences. HuA is a predominantly nuclear protein that can also be found in the cytoplasm of resting T lymphocytes. Within I h after stimulation of T lymphocytes with anti-T cell receptor antibodies or a combination of a phorbol myristate acetate and ionomycin, an increase in cytoplasmic HuA RNA-binding activity was observed. Although absent in resting cells, cytoplasmic tristetraprolin protein was detected 3-6 h following activation. HuA recognized specific AU-rich sequences found in c-jun or c-myc mRNA that were poorly recognized by tristetraprolin. In contrast, tristetraprolin recognized an AU-rich sequence in interleukin-2 mRNA that was poorly recognized by HuA. Both HuA and tristetraprolin, however, recognized AU-rich sequences from ic-fos, interleukin-3, tumor necrosis factor-alpha, and granulocyte/macrophage colony-stimulating factor mRNA. HuA may transiently stabilize a subset of AU-rich element-containing transcripts following T lymphocyte activation, and tristetraprolin may subsequently mediate their degradation.