PSF controls expression of histone variants and cellular viability in thymocytes.
PSF controls expression of histone variants and cellular viability in thymocytes.
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DOI：
10.1016/j.bbrc.2011.09.149
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发表时间：
2011-11-04
影响因子：
3.1
通讯作者：
Lynch, Kristen W.
中科院分区：
文献类型：
--
作者：
Heyd, Florian;Lynch, Kristen W.
即使有了组织限制性基因敲除，研究体内必需的多功能蛋白的作用也常常因细胞活力的完全丧失而变得复杂。在这里，我们利用敲低的方法来研究胸腺细胞中的必需蛋白PSF（多嘧啶道结合蛋白相关剪接因子）的功能。PSF是一种RNA和DNA结合蛋白，在RNA生物合成的各个方面都有作用，从转录到稳定性。我们发现，在胸腺中PSF的表达减少50%，导致细胞凋亡的增加和胸腺细胞结构的相应减少。使用微阵列，我们发现，胸腺细胞耗尽PSF显示相对于野生型同窝仔可能由于mRNA稳定性降低的几个组蛋白基因的表达降低。值得注意的是，这些组蛋白基因中的特定一个（来自组蛋白簇1的H2AE）的表达降低足以诱导培养的T细胞系的凋亡。因此，我们得出结论，PSF有助于组蛋白基因的一个子集的稳定性和H2AE表达的PSF缺陷的胸腺细胞中的损失独特的胸腺细胞凋亡的增加。
Even with the availability of tissue-restricted knockouts, studying the role of essential, multifunctional proteins in vivo is often complicated by the complete loss of cell viability. Here we make use of a knock-down approach to investigate the function of the essential protein PSF (Polypyrimidine tract binding protein-associated Splicing Factor) in thymocytes. PSF is an RNA- and DNA-binding protein that has roles in all aspects of RNA biogenesis from transcription to stability. We show that a 50% reduction in expression of PSF in the thymus leads to an increase in apoptosis and a corresponding decrease in thymic cellularity. Using microarrays we find that thymocytes depleted of PSF show reduced expression of several histone genes relative to wildtype littermates likely due to reduced mRNA stability. Remarkably, reduced expression of a specific one of these histone genes (H2AE from histone cluster 1) is sufficient to induce apoptosis of a cultured T cell line. Therefore, we conclude that PSF contributes to the stability of a subset of histone genes and that loss of H2AE expression in the PSF-deficient thymocytes uniquely contributes to an increase in thymic apoptosis.
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
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通讯作者：
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