Auxiliary splice factor U2AF26 and transcription factor Gfi1 cooperate directly in regulating CD45 alternative splicing
Auxiliary splice factor U2AF26 and transcription factor Gfi1 cooperate directly in regulating CD45 alternative splicing
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DOI：
10.1038/ni1361
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发表时间：
2006-08-01
影响因子：
30.5
通讯作者：
Moeroey, Tarik
中科院分区：
文献类型：
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作者：
Heyd, Florian;ten Dam, Gerdy;Moeroey, Tarik
通过选择性剪接，产生跨膜酪氨酸磷酸酶CD45的不同同种型，其增强或限制T细胞受体信号传导。我们在这里报告，CD45的选择性剪接调控的剪接因子U2AF26和转录因子Gfi1的合作行动。U2AF26通过促进外显子排除促进活性较低的CD45RO的形成。Gfi1通过直接与U2AF 26相互作用来拮抗该过程，确定了转录因子和可变剪接之间的先前未知的联系。Gfi1的存在导致更活跃的CD45 RB的形成，而Gfi1的缺失有利于CD45 RO的产生。我们认为U2AF26和Gfi1的相对丰度决定了CD45亚型的比例，从而调节T细胞活化。
By alternative splicing, different isoforms of the transmembrane tyrosine phosphatase CD45 are generated that either enhance or limit T cell receptor signaling. We report here that CD45 alternative splicing is regulated by cooperative action of the splice factor U2AF26 and the transcription factor Gfi1. U2AF26 promoted formation of the less-active CD45RO by facilitating exon exclusion. Gfi1 antagonized that process by directly interacting with U2AF26, identifying a previously unknown link between a transcription factor and alternative splicing. The presence of Gfi1 led to formation of the more-active CD45RB, whereas loss of Gfi1 favored CD45RO production. We propose that the relative abundance of U2AF26 and Gfi1 determines the ratio of CD45 isoforms, thereby regulating T cell activation.