The power of fission: yeast as a tool for understanding complex splicing.

The power of fission: yeast as a tool for understanding complex splicing.
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DOI:
10.1007/s00294-016-0647-6
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发表时间:
2017-06
期刊:
影响因子:
2.5
通讯作者:
Pleiss JA
Pleiss JA
中科院分区:
生物学3区
文献类型:
--
作者:
Fair BJ;Pleiss JA

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Pre-mRNA 剪接是真核基因表达的重要组成部分。许多后生动物,包括人类,调节选择性剪接模式,以从有限数量的基因中产生蛋白质组的扩展。重要的是,相当一部分导致人类疾病的突变是通过改变形成基因剪接模式的序列来表现出来的。因此,了解这一复杂途径的机制基础将是对抗这些疾病的重要组成部分。几乎可以追溯到剪接的最初发现,研究人员就利用芽殖酵母的遗传易处理性来识别其成分并破译剪接机制。然而,芽殖酵母缺乏与人类最相关的复杂剪接机制和选择性剪接模式。最近,许多研究人员将精力转向研究裂殖酵母,裂殖酵母,它保留了复杂剪接的许多特征,包括简并剪接位点序列、外显子剪接增强子的使用和SR蛋白。在这里,我们回顾了最近使用裂变酵母遗传学来检查前 mRNA 剪接的工作,强调了其对模拟高等真核生物中复杂剪接的前景。
Pre-mRNA splicing is an essential component of eukaryotic gene expression. Many metazoans, including humans, regulate alternative splicing patterns to generate expansions of their proteome from a limited number of genes. Importantly, a considerable fraction of human disease causing mutations manifest themselves through altering the sequences that shape the splicing patterns of genes. Thus, understanding the mechanistic bases of this complex pathway will be an essential component of combating these diseases. Dating almost to the initial discovery of splicing, researchers have taken advantage of the genetic tractability of budding yeast to identify the components and decipher the mechanisms of splicing. However, budding yeast lacks the complex splicing machinery and alternative splicing patterns most relevant to humans. More recently, many researchers have turned their efforts to study the fission yeast, Schizosaccharomyces pombe, which has retained many features of complex splicing, including degenerate splice site sequences, the usage of exonic splicing enhancers, and SR proteins. Here, we review recent work using fission yeast genetics to examine pre-mRNA splicing, highlighting its promise for modeling the complex splicing seen in higher eukaryotes.