Context-dependent control of alternative splicing by RNA-binding proteins.

Context-dependent control of alternative splicing by RNA-binding proteins.
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DOI:
10.1038/nrg3778
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发表时间:
2014-10
期刊:
Nature reviews. Genetics
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序列特异性rna结合蛋白(rbp)与pre-mRNA结合以控制选择性剪接,但目前还不可能读取根据基因组序列指示剪接调节的“剪接代码”。每个可选剪接事件由多个rbp控制,它们的联合作用在给定的细胞类型中产生可选剪接产物的分布。由于每种细胞类型表达不同的rbp序列,因此对给定RNA靶标的调控信息的解释非常依赖于细胞类型。rbp还在许多层面上控制彼此的功能,包括通过相互调节它们在特定调控RNA元件上的结合活性。在这篇综述中,我们描述了一些新出现的规则,这些规则支配着高度依赖上下文和组合性质的选择性剪接调节。
Sequence-specific RNA-binding proteins (RBPs) bind to pre-mRNA to control alternative splicing, but it is not yet possible to read the ‘splicing code’ that dictates splicing regulation on the basis of genome sequence. Each alternative splicing event is controlled by multiple RBPs, the combined action of which creates a distribution of alternatively spliced products in a given cell type. As each cell type expresses a distinct array of RBPs, the interpretation of regulatory information on a given RNA target is exceedingly dependent on the cell type. RBPs also control each other’s functions at many levels, including by mutual modulation of their binding activities on specific regulatory RNA elements. In this Review, we describe some of the emerging rules that govern the highly context-dependent and combinatorial nature of alternative splicing regulation.
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