Functional roles of alternative splicing factors in human disease.
Functional roles of alternative splicing factors in human disease.
复制标题
DOI：
10.1002/wrna.1276
复制
发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
Carstens RP
中科院分区：
文献类型：
--
作者：
Cieply B;Carstens RP
选择性剪接(AS)是从有限的基因组中产生更大的转录和蛋白质组多样性的重要机制。几乎所有的人类基因转录本都是选择性剪接的，可以产生具有不同甚至拮抗特性的蛋白质异构体，从而影响细胞功能。许多AS事件在不同的发育阶段以细胞类型或组织特异性的方式受到严格调控。AS由RNA结合蛋白调控，包括细胞或组织特异性剪接因子。在过去的几年里，技术的进步定义了基因组范围的程序，如由越来越多的剪接因子调节的。这些剪接调控网络(SRN)由转录本组成，编码的蛋白质在影响不同细胞类型的发育和表型的协调和相关过程中发挥功能。因此，人们越来越认识到，受不同剪接因子调控的正常剪接程序的中断可能会导致人类疾病。我们将总结剪接调节蛋白表达或功能改变与人类疾病病理生理学有关的疾病的例子。随着AS在人类疾病和疾病风险中的作用不断被揭示，人们希望进一步研究众多剪接因子的功能及其调节的靶点，将能够开发针对特定AS事件及其影响的生物途径的新疗法。《电线RNA 2015》，6：311-326。DOI：10.1002/wrna.1276有关本文的更多资源，请访问http://wires.wiley.com/remdoi.cgi?doi=10.1002/wrna.1276WIREs网站。利益冲突：作者声明本文没有利益冲突。
Alternative splicing (AS) is an important mechanism used to generate greater transcriptomic and proteomic diversity from a finite genome. Nearly all human gene transcripts are alternatively spliced and can produce protein isoforms with divergent and even antagonistic properties that impact cell functions. Many AS events are tightly regulated in a cell-type or tissue-specific manner, and at different developmental stages. AS is regulated by RNA-binding proteins, including cell- or tissue-specific splicing factors. In the past few years, technological advances have defined genome-wide programs of AS regulated by increasing numbers of splicing factors. These splicing regulatory networks (SRNs) consist of transcripts that encode proteins that function in coordinated and related processes that impact the development and phenotypes of different cell types. As such, it is increasingly recognized that disruption of normal programs of splicing regulated by different splicing factors can lead to human diseases. We will summarize examples of diseases in which altered expression or function of splicing regulatory proteins has been implicated in human disease pathophysiology. As the role of AS continues to be unveiled in human disease and disease risk, it is hoped that further investigations into the functions of numerous splicing factors and their regulated targets will enable the development of novel therapies that are directed at specific AS events as well as the biological pathways they impact. WIREs RNA 2015, 6:311–326. doi: 10.1002/wrna.1276 For further resources related to this article, please visit the http://wires.wiley.com/remdoi.cgi?doi=10.1002/wrna.1276WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.