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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Conservation in budding yeast of a kinase specific for SR splicing factors
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Conservation in budding yeast of a kinase specific for SR splicing factors

机译:SR剪接因子特异的激酶在发芽酵母中的保守性

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摘要

SR protein kinases (SRPKs) and their substrates, the SR family of serine/ arginine-rich pre-mRNA splicing factors, appear to be key regulators of alternative splicing. Although SR proteins have been well characterized through biochemical experiments in metazoans, their functions in vivo are unclear. Because of the strict splice site consensus and near absence of alternative splicing in Saccharomyces cerevisiae, it had been thought that budding yeast would lack an SRPK and its substrates. Here, we present structural, biochemical, and cell-biological evidence that directly demonstrates an SR protein kinase, Skylp, as well as a number of SRPK substrates in S. cerevisiae. One of these substrates is Npl3p, an SR-like protein involved in mRNA export. This finding raises the provocative possibility that Skylp, and by extension metazoan SPRKs, regulates mRNA export or the nucleocytoplasmic shuttling of RS domain proteins. The unexpected discovery of an SR protein kinase in budding yeast provides a foundation for genetic dissection of the biological functions of SR proteins and their kinases.
机译:SR蛋白激酶(SRPK)及其底物,富含丝氨酸/精氨酸的pre-mRNA剪接因子的SR系列,似乎是替代剪接的关键调控因子。尽管通过后生动物的生化实验已经很好地表征了SR蛋白,但它们在体内的功能尚不清楚。由于严格的剪接位点共有,并且在酿酒酵母中几乎没有其他剪接,因此人们认为出芽的酵母将缺少SRPK及其底物。在这里,我们提供结构,生化和细胞生物学的证据,这些证据直接证明了酿酒酵母中的SR蛋白激酶Skylp和许多SRPK底物。这些底物之一是Npl3p,一种参与mRNA输出的SR样蛋白。这一发现提高了Skylp的可能性,并通过后生动物SPRKs调节mRNA的输出或RS结构域蛋白的核质穿梭。在出芽酵母中意外发现SR蛋白激酶为SR蛋白及其激酶的生物学功能的遗传解剖奠定了基础。

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