Global coordination of transcriptional control and mRNA decay during cellular differentiation.
Global coordination of transcriptional control and mRNA decay during cellular differentiation.
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DOI：
10.1038/msb.2010.38
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发表时间：
2010-06-08
影响因子：
9.9
通讯作者：
Mata, Juan
中科院分区：
文献类型：
--
作者：
Amorim, Maria J.;Cotobal, Cristina;Duncan, Caia;Mata, Juan
转录在动态基因表达程序中的功能已被广泛研究，但对其如何在全基因组水平上与RNA周转整合知之甚少。我们使用裂殖酵母减数分裂基因表达程序研究了这些问题。我们鉴定了超过80种与减数分裂特异性Meu5p RNA结合蛋白共纯化的转录物。它们的水平和半衰期在meu5突变体中降低，表明Meu5p稳定其靶标。大多数Meu5p结合的RNA也是Mei4p转录因子的靶点，Mei4p转录因子诱导Mei500减数分裂基因的瞬时表达。虽然许多Mei4p靶标显示尖锐的表达峰，但Meu5p靶标具有广泛的表达谱。在不存在meu5的情况下，所有Mei4p靶标以相似的动力学表达，表明Meu5p改变了基因表达程序的全局特征。由于Mei4p激活Meu5转录，Mei4p，Meu5p和它们的共同靶点形成前馈环，这是转录网络中常见的基序，但在mRNA衰变的背景下没有研究。我们的数据提供了深入了解整合转录和转录后控制的调控网络的拓扑结构。
The function of transcription in dynamic gene expression programs has been extensively studied, but little is known about how it is integrated with RNA turnover at the genome-wide level. We investigated these questions using the meiotic gene expression program of Schizosaccharomyces pombe. We identified over 80 transcripts that co-purify with the meiotic-specific Meu5p RNA-binding protein. Their levels and half-lives were reduced in meu5 mutants, demonstrating that Meu5p stabilizes its targets. Most Meu5p-bound RNAs were also targets of the Mei4p transcription factor, which induces the transient expression of ∼500 meiotic genes. Although many Mei4p targets showed sharp expression peaks, Meu5p targets had broad expression profiles. In the absence of meu5, all Mei4p targets were expressed with similar kinetics, indicating that Meu5p alters the global features of the gene expression program. As Mei4p activates meu5 transcription, Mei4p, Meu5p and their common targets form a feed-forward loop, a motif common in transcriptional networks but not studied in the context of mRNA decay. Our data provide insight into the topology of regulatory networks integrating transcriptional and posttranscriptional controls.
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