Developments in RNA Splicing and Disease
Developments in RNA Splicing and Disease
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DOI：
10.1101/cshperspect.a000778
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发表时间：
2011-01-01
影响因子：
7.2
通讯作者：
Swanson, Maurice S.
中科院分区：
文献类型：
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作者：
Poulos, Michael G.;Batra, Ranjan;Swanson, Maurice S.
mRNA 前处理，包括 5' 末端加帽、剪接、编辑和多腺苷酸化，由一系列精心策划的主要共转录步骤组成，确保真核基因表达的高保真度和极端多样性特征。选择性剪接和编辑允许相对较小的基因组编码大量蛋白质组阵列，而选择性 3' 末端形成可以实现 mRNA 定位、翻译和稳定性的变化。当然，这种机械复杂性的代价很高。调节 mRNA 生物合成的无数 RNA 序列元件以及作用于这些序列的反式作用因子的突变是许多人类疾病的基础。在这篇综述中，我们重点关注这些关键的 RNA 加工步骤之一，即剪接，以强调最近的研究，这些研究描述了肌肉和神经系统疾病的传统和新型致病机制。
Pre-mRNA processing, including 5'-end capping, splicing, editing, and polyadenylation, consists of a series of orchestrated and primarily cotranscriptional steps that ensure both the high fidelity and extreme diversity characteristic of eukaryotic gene expression. Alternative splicing and editing allow relatively small genomes to encode vast proteomic arrays while alternative 3'-end formation enables variations in mRNA localization, translation, and stability. Of course, this mechanistic complexity comes at a high price. Mutations in the myriad of RNA sequence elements that regulate mRNA biogenesis, as well as the trans-acting factors that act upon these sequences, underlie a number of human diseases. In this review, we focus on one of these key RNA processing steps, splicing, to highlight recent studies that describe both conventional and novel pathogenic mechanisms that underlie muscle and neurological diseases.