RNA-Binding Proteins: Splicing Factors and Disease.
RNA-Binding Proteins: Splicing Factors and Disease.
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DOI：
10.3390/biom5020893
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发表时间：
2015-05-13
期刊：
影响因子：
5.5
通讯作者：
Fairbrother WG
中科院分区：
文献类型：
--
作者：
Fredericks AM;Cygan KJ;Brown BA;Fairbrother WG
Pre-mRNA剪接是由核心剪接体和一系列辅助RNA结合蛋白与顺式序列元件的相互作用介导的。剪接是高等真核生物的主要调控成分。剪接中断是人类疾病的主要原因。三分之一的遗传性疾病等位基因被认为会导致异常剪接。遗传性疾病等位基因可以通过破坏剪接元件、产生有毒RNA或影响剪接因子来改变剪接。医学遗传学面临的挑战之一是从临床测序实验中发现的数千种可能性中识别出因果变异。在这里，我们回顾了剪接的基本生物化学，剪接突变的机制，剪接突变的鉴定方法，以及治疗干预的潜力。
Pre-mRNA splicing is mediated by interactions of the Core Spliceosome and an array of accessory RNA binding proteins with cis-sequence elements. Splicing is a major regulatory component in higher eukaryotes. Disruptions in splicing are a major contributor to human disease. One in three hereditary disease alleles are believed to cause aberrant splicing. Hereditary disease alleles can alter splicing by disrupting a splicing element, creating a toxic RNA, or affecting splicing factors. One of the challenges of medical genetics is identifying causal variants from the thousands of possibilities discovered in a clinical sequencing experiment. Here we review the basic biochemistry of splicing, the mechanisms of splicing mutations, the methods for identifying splicing mutants, and the potential of therapeutic interventions.