RNA binding protein regulated differentiation- dependent alternative splicing

选择性剪接是产生具有不同稳定性、翻译效率或蛋白质编码序列的多个mrna的常见机制。外显子的选择通常受细胞类型特异性或分化状态依赖性剪接机制的控制。外显子选择的效率取决于几个决定因素的平衡，如剪接供体和受体位点序列，外显子大小，外显子和内含子中的增强子和抑制子，以及竞争剪接位点序列的相对潜力。目前已知的大多数顺式调控元件都参与了本构剪接途径。在哺乳动物基因中，只有有限数量的顺式元件参与选择性剪接已被报道。我们在NCAM（神经细胞粘附分子）基因的MSDb（肌肉特异性结构域b）下游发现了一个内含子顺式作用元件。顺式元件在非肌肉成纤维细胞中作为外显子MSDb选择的负调节因子，而在已经注定要分化为肌肉细胞的成肌细胞中则不是。该顺式元件对MSDb外显子选择的抑制作用在肌发生过程中得到释放。我们搜索了与顺作用元件（如剪接因子和调节因子）结合的反作用因子。

Alternative splicing is a comon mechanism for the generation of multiple mRNAs with different stabilities, translation efficiencies, or protein coding sequences from a single gene. The selection of an alternative exon is often under the control of cell type-specific or differentiation state-dependent splicing machinery. The efficiency of exon selection is determined by a balance of several determinants, such as splice donor and acceptor site sequences, exon size, enhancer and repressor resided in exons and intron, and relative potentials of competing splice site sequences. Most of the cis-acting regulatory elements characterized up to date involved in a constitutive splicing pathway. In mammalian genes, only a limited number of cis-elements that participate in the alternative splicing has been reported. We found for an intronic cis-acting element located downstrem exon MSDb (muscle-specific domain b) in the NCAM (neural cell adhesion molecule) gene. The cis-element acted as a negative regulator for the selection of exon MSDb in nonmuscle fibroblast but not in myoblasts, that are already destined to differentiate into muscle cells. The suppressive effect of this cis-element on the selection of exon MSDb was released in the process of myogenesis. We searched for trans-acting factor (s) that bind to the cisacting elements, such as splicing factors and regulators.