核前体mRNA的剪接与视网膜色素变性

Pre-mRNA splicing and retinitis pigmentosa

视网膜色素变性（RP）是一组常见的遗传性视网膜变性疾病，具有高度的遗传异质性。在超过40个不同种类的RP致病基因中包括一部分全身广泛表达的基因，最具代表性的为5个核前体mRNA（pre—mRNA）的剪接相关基因。在RP基因的最新研究中，人们认识到核前体mRNA剪切缺陷在常染色体显性遗传RP（adRP）病因学中占有非常重要地位，同时也使人们对核前体mRNA剪切这一基本的生物学过程有了更清楚的认识。目前，人们在此领域的研究主要集中在两个方面：（1）adRP相关的核前体mRNA剪切基因（adRP-剪接因子）突变如何影响核前体mRNA剪切功能。（2）这些全身表达的基因变异为何特异性地引起视网膜病变。这两个研究主题也恰恰吻合了此类疾病发病机制中的前后两个重要环节。近年来，人们已经在第一个研究主题中取得了显著的进步，第5个adRP-剪接因子SNRNP200基因的克隆及其相关功能研究是此研究方向的重要进步之一。在第二个研究主题中人们也进行了大量的工作，各种生物模型的建立使得人们对疾病的病理过程有了更清晰的描述，然而在关键的发病机制问题上依然面临着许多令人迷惑的问题。总结adRP-剪接因子的最新研究成果，重点阐述核前体mRNA的剪接缺陷引发RP的分子机制研究中亟待解决的问题。

Retinitis pigmentosa （RP） is a large group of common hereditary eye diseases with highly heterogeneous genetic background. Over forly genes with diverse functionalities are associated with RP and they include a set of ubiquitously expressed genes. These include five genes involved in the precursor messenger RNA（ pre- mRNA） splicing. Recent progress in disease gene identification for RP has established the involvement of pre-mRNA splicing as one important mechanism in the disease etiology and has shed light on the splicing process itself, a fundamental biological process. To this date, studies in this field have been focused on two major issues. First, how do the mutations of the adRP associated splicing factors （adRP-SF） affect the splicing function？ Second, how do the mutations in these ubiquitously expressed genes lead to specific retinopathy？ The two topics fit with the two continuous important steps of the disease pathogenesis. Recently,researchers have made a dramatic progress in the first topic. The identification of the SNRNP200 gene,the fifth adRP-SF and its relevant functional study has shown significance to the progress in the study of RP. Numerous investigations are also being carried out in addressing the second issue. Generation of a wtriety of models led to a better description of the pathological process of the disease. However, in respect to the key pathogenic mechanism,researchers are still puzzled with a number of confusing questions. In this commentary, the results from the latest investigations were summarized, and in particular, the difficulties in studying the molecular mechanism by which the pre-mRNA splicing deficiency causes RP were detailed.