RNA 结合蛋白对可变剪接的上下文依赖性调控。
Context-dependent control of alternative splicing by RNA-binding proteins.
机构信息
Department of Cellular and Molecular Medicine and Institute for Genomic Medicine, University of California San Diego, La Jolla, California 92093-0651, USA.
Center for Molecular Biology of RNA, and Department of Molecular, Cell, and Developmental Biology, University of California at Santa Cruz, Santa Cruz, California 95064, USA.
出版信息
Nat Rev Genet. 2014 Oct;15(10):689-701. doi: 10.1038/nrg3778. Epub 2014 Aug 12.
Abstract
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.
摘要
序列特异性 RNA 结合蛋白（RBPs）与前体 mRNA 结合以控制可变剪接，但目前还无法根据基因组序列解读决定剪接调控的“剪接密码”。每个可变剪接事件都受到多个 RBPs 的控制，它们的共同作用在给定的细胞类型中产生了可变剪接产物的分布。由于每个细胞类型都表达一组独特的 RBPs，因此对特定 RNA 靶标上的调控信息的解释极大地依赖于细胞类型。RBPs 还在多个层面上相互控制彼此的功能，包括通过相互调节它们在特定调节 RNA 元件上的结合活性。在这篇综述中，我们描述了一些新兴的规则，这些规则支配着可变剪接调控的高度上下文相关和组合性质。
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