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Abstract：
Neurons make extensive use of alternative pre-mRNA splicing to regulate gene expression and diversify physiological responses. We showed previously in a pituitary cell line that the Ca(++)/calmodulin-dependent protein kinase CaMK IV specifically repressed splicing of the BK channel STREX exon. This repression is dependent on a CaMK IV-responsive RNA element (CaRRE) within the STREX 3\' splice site. Here, we report that similar Ca(++) regulation of splicing, mediated by L-type calcium channels and CaM kinase IV, occurs in cultured neurons and in the brain. We identify a critical CaRRE motif (CACATNRTTAT) that is essential for conferring CaMK IV repression on an otherwise constitutive exon. Additional Ca(++)-regulated exons that carry this consensus sequence are also identified in the human genome. Thus, the Ca(++)/CaMK IV pathway in neurons controls the alternative splicing of a group of exons through this short CaRRE consensus sequence. The functions of some of these exons imply that splicing control through the CaMK IV pathway will alter neuronal activity.
摘要：
神经元广泛使用选择性pre-mRNA剪接来调节基因表达并使生理反应多样化。我们先前在垂体细胞系中显示，Ca（）/钙调蛋白依赖性蛋白激酶CaMKIV特异性抑制了BK通道STREX外显子的剪接。这种抑制依赖于STREX3'剪接位点内的CaMKIV反应性RNA元件(CaRRE)。这里,我们报道了类似的Ca（++）剪接调节，由L型钙通道和CaM激酶IV介导，发生在培养的神经元和大脑中。我们确定了关键的CaRRE基序（CACATNRTTAT），该基序对于在其他组成型外显子上赋予CaMKIV抑制至关重要。在人类基因组中还鉴定了携带该共有序列的其他Ca(++)调节的外显子。因此，神经元中的Ca（++）/CaMKIV途径通过该短的CaRRE共有序列控制一组外显子的可变剪接。这些外显子中的一些的功能意味着通过CaMKIV途径的剪接控制将改变神经元活性。
