CELF6, a member of the CELF family of RNA-binding proteins, regulates muscle-specific splicing enhancer-dependent alternative splicing
CELF6, a member of the CELF family of RNA-binding proteins, regulates muscle-specific splicing enhancer-dependent alternative splicing
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DOI：
10.1074/jbc.m310687200
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发表时间：
2004-04-23
影响因子：
4.8
通讯作者：
Cooper, TA
中科院分区：
文献类型：
--
作者：
Ladd, AN;Nguyen, NH;Cooper, TA
我们以前描述了一个五种RNA结合蛋白的家族：CUG结合蛋白，胚胎致死异常视觉型RNA结合蛋白3，以及CUG结合蛋白和胚胎致死异常视觉型RNA结合蛋白3样因子（CELF）3，4和5。我们证明，所有这五种蛋白质特异性激活外显子纳入心肌肌钙蛋白T小基因在体内通过肌肉特异性剪接增强子（MSE）序列。我们还预测第六个家族成员CELF 6位于15号染色体上。在这里，我们描述了CELF 6的分离和表征。与先前描述的CELF蛋白一样，CELF 6共享包含三个RNA结合结构域和未知功能的发散结构域的结构域结构。CELF 6在肾脏、脑和睾丸中强烈表达，并且在大多数其他组织中以非常低的水平表达。在大脑中，表达是广泛的，并从胎儿到成人保持。CELF 6在瞬时转染试验中以MSE依赖性方式激活心肌肌钙蛋白T小基因的外显子包含，并且可以通过单个元件MSE 2的多个拷贝激活包含。这些结果将CELF 6置于包括CELF 3、4和5的CELF蛋白的功能亚家族中。CELF 6还促进胰岛素受体外显子11的跳跃，这是在肾脏中表达的CELF活性的已知靶标。
We previously described a family of five RNA-binding proteins: CUG-binding protein, embryonic lethal abnormal vision-type RNA-binding protein 3, and the CUG-binding protein and embryonic lethal abnormal vision-type RNA-binding protein 3-like factors (CELFs) 3, 4, and 5. We demonstrated that all five of these proteins specifically activate exon inclusion of cardiac troponin T minigenes in vivo via muscle-specific splicing enhancer (MSE) sequences. We also predicted that a sixth family member, CELF6, was located on chromosome 15. Here, we describe the isolation and characterization of CELF6. Like the previously described CELF proteins, CELF6 shares a domain structure containing three RNA-binding domains and a divergent domain of unknown function. CELF6 is strongly expressed in kidney, brain, and testis and is expressed at very low levels in most other tissues. In the brain, expression is widespread and maintained from the fetus to the adult. CELF6 activates exon inclusion of a cardiac troponin T minigene in transient transfection assays in an MSE-dependent manner and can activate inclusion via multiple copies of a single element, MSE2. These results place CELF6 in a functional subfamily of CELF proteins that includes CELFs 3, 4, and 5. CELF6 also promotes skipping of exon 11 of insulin receptor, a known target of CELF activity that is expressed in kidney.