Gaur Rajesh K
Division of Molecular Biology, Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
Biotechniques. 2006 Apr;Suppl:15-22. doi: 10.2144/000112165.
Alternative splicing of precursor messenger RNAs (pre-mRNAs) is one of the most important sources of protein diversity in vertebrates. An estimated 35%-70% of human genes generate transcripts that are alternatively spliced, and defects in this process are linked to numerous human genetic diseases and various forms of cancer. The discovery that 21-23 nucleotide RNA duplexes, known as small interfering RNAs (siRNAs), can knockdown the homologous mRNAs in mammalian cells has revolutionized many aspects of drug discovery including down-regulation of disease-associated splicing isoforms. In addition, RNA interference (RNAi)-mediated silencing of splicing regulators has the potential to define the complex network of alternative splicing regulation and to analyze gene function. In this review, I first provide a brief introduction to mRNA splicing and its relationship to human diseases. This is followed by a brief overview of RNAi. Finally I discuss the therapeutic potential of RNAi in targeting disease-linked splicing isoforms.
前体信使核糖核酸（pre-mRNA）的可变剪接是脊椎动物中蛋白质多样性最重要的来源之一。据估计，35%-70%的人类基因会产生可变剪接的转录本，这一过程中的缺陷与众多人类遗传疾病和各种癌症相关。21-23个核苷酸的RNA双链体，即小干扰RNA（siRNA），能够在哺乳动物细胞中敲低同源mRNA，这一发现彻底改变了药物研发的许多方面，包括下调与疾病相关的剪接异构体。此外，RNA干扰（RNAi）介导的剪接调节因子沉默有潜力界定可变剪接调控的复杂网络并分析基因功能。在这篇综述中，我首先简要介绍mRNA剪接及其与人类疾病的关系。接下来简要概述RNAi。最后，我将讨论RNAi在靶向与疾病相关的剪接异构体方面的治疗潜力。
