Department of Molecular Genetics, Cleveland Clinic, Cleveland, OH, USA.
Trends Genet. 2012 Apr;28(4):147-54. doi: 10.1016/j.tig.2012.01.001. Epub 2012 Mar 5.
The removal by splicing of introns from the primary transcripts of most mammalian genes is an essential step in gene expression. Splicing is performed by large, complex ribonucleoprotein particles termed spliceosomes. Mammals contain two types that splice out mutually exclusive types of introns. However, the role of the minor spliceosome has been poorly studied. Recent reports have now shown that mutations in one minor spliceosomal snRNA, U4atac, are linked to a rare autosomal recessive developmental defect. In addition, very exciting recent results of exome deep-sequencing have found that recurrent, somatic, heterozygous mutations of other splicing factors occur at high frequencies in particular cancers and pre-cancerous conditions, suggesting that alterations in the core splicing machinery can contribute to tumorigenesis. Mis-splicing of crucial genes may underlie the pathologies of all of these diseases. Identifying these genes and understanding the mechanisms involved in their mis-splicing may lead to advancements in diagnosis and treatment.
大多数哺乳动物基因的初级转录本中内含子的剪接去除是基因表达的一个必要步骤。剪接是由称为剪接体的大型复杂核糖核蛋白颗粒完成的。哺乳动物含有两种类型，可剪接出相互排斥的两种内含子。然而，对小剪接体的作用研究甚少。最近的报告表明，一种小剪接体 snRNA（U4atac）中的突变与一种罕见的常染色体隐性发育缺陷有关。此外，外显子深度测序的非常令人兴奋的最新结果发现，在某些癌症和癌前状态中，其他剪接因子的复发性、体细胞、杂合突变以高频率发生，这表明核心剪接机制的改变可能有助于肿瘤发生。关键基因的错误剪接可能是这些疾病病理的基础。鉴定这些基因并了解其错误剪接涉及的机制可能会推动诊断和治疗的进展。
