Concentration-dependent control of pyruvate kinase M mutually exclusive splicing by hnRNP proteins.
Concentration-dependent control of pyruvate kinase M mutually exclusive splicing by hnRNP proteins.
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DOI：
10.1038/nsmb.2219
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发表时间：
2012-02-05
影响因子：
16.8
通讯作者：
Manley, James L.
中科院分区：
文献类型：
--
作者：
Chen, Mo;David, Charles J.;Manley, James L.
哺乳动物丙酮酸激酶M （PKM）基因的表达是互斥剪接的一个重要例子。我们之前已经证明hnRNP蛋白A1、A2和PTB在这一过程中起着关键作用。在这里，我们提供的证据表明，涉及这些蛋白质网络的浓度依赖性相互作用足以决定PKM剪接的结果。高浓度时，如在大多数癌细胞中发现的，hnRNP A1结合到上游调控外显子（外显子9）的两个位点，协调合作相互作用，导致外显子9被排斥。在较低浓度下，结合转移到下游的内含子位点，如外显子9被包括在内，而外显子10基本上被排除在外，任何包含两个外显子的mRNA都被无义介导的衰变降解。总之，我们的研究结果提供了一种机制，通过这种机制，少数一般因子控制广泛表达的转录物的选择性剪接。
Expression of the mammalian pyruvate kinase M (PKM) gene provides an important example of mutually exclusive splicing. We showed previously that the hnRNP proteins A1, A2 and PTB play a critical role in this process. Here we provide evidence that concentration-dependent interactions involving a network of these proteins are sufficient to determine the outcome of PKM splicing. At high concentrations, such as found in most cancer cells, hnRNP A1 binding to two sites in the upstream regulated exon (exon 9) orchestrates cooperative interactions leading to exon 9 exclusion. At lower concentrations, binding shifts to downstream intronic sites such that exon 9 is included and exon 10 largely excluded, with any mRNA including both exons degraded by nonsense-mediated decay. Together our results provide a mechanism by which a small number of general factors control alternative splicing of a widely expressed transcript.
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影响因子：
64.5
作者：
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通讯作者：
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DOI：
10.1073/pnas.0700343104
发表时间：
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影响因子：
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作者：
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通讯作者：
Manley, James L.
DOI：
10.1073/pnas.0914845107
发表时间：
2010-02-02
影响因子：
11.1
作者：
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通讯作者：
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