Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs.
Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs.
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DOI：
10.1038/cdd.2013.135
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发表时间：
2014-01
影响因子：
12.4
通讯作者：
中科院分区：
文献类型：
--
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基因表达的转录后控制由RNA结合蛋白与其同源mRNA的相互作用介导，所述同源mRNA特异性地调节其稳定性、定位和翻译。mRNA结合蛋白是多功能的，因此已经提出存在允许特定蛋白质亚复合物在一系列病理生理条件下控制细胞质基因表达的组合RNA结合蛋白密码。我们发现，多聚嘧啶道结合蛋白（PTB）是中央的一个这样的复合物，在凋亡细胞中形成。因此，在由TNF相关的凋亡诱导配体启动的凋亡过程中，PTB与之相互作用的RNA结合蛋白的库发生变化。我们表明，改变PTB及其结合伙伴的细胞水平，无论是单独或组合，足以直接改变细胞凋亡率与PTB，YBX 1，PSF和NONO/p54 nrb的表达增加加速这一进程。从机制上讲，我们表明，这些蛋白质转录后调节基因表达，因此凋亡率，通过相互作用和刺激的RNA元件（内部核糖体进入段）的活性，发现在mRNA的翻译过程中凋亡。总之，我们的数据表明，PTB功能是由一组共同招募的蛋白质控制，重要的是提供了进一步的证据，它是可能的，通过单独调节细胞质基因表达途径来决定细胞的命运。
Post-transcriptional control of gene expression is mediated by the interaction of RNA-binding proteins with their cognate mRNAs that specifically regulate their stability, localization and translation. mRNA-binding proteins are multifunctional and it has been proposed therefore that a combinatorial RNA-binding protein code exists that allows specific protein sub-complexes to control cytoplasmic gene expression under a range of pathophysiological conditions. We show that polypyrimidine tract-binding protein (PTB) is central to one such complex that forms in apoptotic cells. Thus, during apoptosis initiated by TNF-related apoptosis inducing ligand there is a change in the repertoire of RNA-binding proteins with which PTB interacts. We show that altering the cellular levels of PTB and its binding partners, either singly or in combination, is sufficient to directly change the rates of apoptosis with increased expression of PTB, YBX1, PSF and NONO/p54nrb accelerating this process. Mechanistically, we show that these proteins post-transcriptionally regulate gene expression, and therefore apoptotic rates, by interacting with and stimulating the activity of RNA elements (internal ribosome entry segments) found in mRNAs that are translated during apoptosis. Taken together, our data show that PTB function is controlled by a set of co-recruited proteins and importantly provide further evidence that it is possible to dictate cell fate by modulating cytoplasmic gene expression pathways alone.
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影响因子：
5.6
作者：
Le Quesne, JPC;Stoneley, M;Willis, AE
通讯作者：
Willis, AE
影响因子：
5.3
作者：
Pickering, BM;Mitchell, SA;Willis, AE
通讯作者：
Willis, AE
影响因子：
4.8
作者：
Gorospe M;Tominaga K;Wu X;Fähling M;Ivan M
通讯作者：
Ivan M
影响因子：
5.3
作者：
Cobbold, Laura C.;Spriggs, Keith A.;Willis, Anne E.
通讯作者：
Willis, Anne E.
影响因子：
16
作者：
Dickens, Laura S.;Boyd, Robert S.;Jukes-Jones, Rebekah;Hughes, Michelle A.;Robinson, Gemma L.;Fairall, Louise;Schwabe, John W. R.;Cain, Kelvin;MacFarlane, Marion
通讯作者：
MacFarlane, Marion