A novel protein, Pho92, has a conserved YTH domain and regulates phosphate metabolism by decreasing the mRNA stability of PHO4 in Saccharomyces cerevisiae
A novel protein, Pho92, has a conserved YTH domain and regulates phosphate metabolism by decreasing the mRNA stability of PHO4 in Saccharomyces cerevisiae
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DOI：
10.1042/bj20130862
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发表时间：
2014-02-01
影响因子：
4.1
通讯作者：
Yun, Cheol-Won
中科院分区：
文献类型：
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作者：
Kang, Hyun-Jun;Jeong, Sook-Jin;Yun, Cheol-Won
人YTHDF2的同源物Ydr374c(Pho92)是酿酒酵母中唯一含有YT521-B同源结构域的蛋白质。基于基因芯片分析，参与磷酸信号转导(Pho)途径的基因在Delta Pho92菌株中上调，Ph4是pho途径中重要的转录因子。为了确定Pho92作用于磷酸盐代谢的确切机制，我们研究了Pho92对PHO4表达的影响。在Delta Pho92菌株中，PHO4基因的半衰期延长；缺失突变体UPF1和POP2中也观察到了这种表型，它们分别是NMD(无义介导的衰退)途径和Pop2-CCR4-Not Deadenylase复合体的组成部分。Pho92与Pop2-CCR4-非死烯基酶复合体的Pop2物理相互作用。此外，Pho92与PHO4的3‘-UTR的结合依赖于磷酸盐浓度。PHO43‘-UTR的缺失导致PHO4mRNA对依赖于Pho92的降解产生抵抗。本研究的结果表明，Pho92通过调节mRNA的稳定性在转录后水平调节Pho4的表达。综上所述，Pho92参与了细胞的磷酸盐代谢，特别是通过与3‘-UTR结合来调节PHO4的稳定性，这种方式依赖于磷酸盐。
The homologue of human YTHDF2, Ydr374c (Pho92), is the only protein that has a YTH (YT521-B homology) domain in Saccharomyces cerevisiae. Based on microarray analysis, genes involved in the phosphate signal transduction (PHO) pathway were up-regulated in the Delta pho92 strain, as were genes regulated by Pho4, which is an important transcription factor in the PHO pathway. To identify the exact mechanism of Pho92 action with respect to phosphate metabolism, we investigated the effect of Pho92 on PHO4 expression. The half-life of PHO4 mRNA was increased in the Delta pho92 strain; this phenotype was also observed in the deletion mutants UPF1 and POP2, which are components of the NMD (nonsense-mediated decay) pathway and the Pop2-Ccr4-Not deadenylase complex respectively. Pho92 interacts physically with Pop2 of the Pop2-Ccr4-Not deadenylase complex. Furthermore, Pho92 binding to the 3'-UTR of PHO4 was dependent on the phosphate concentration. Deletion of the PHO4 3'-UTR resulted in PHO4 mRNA resistance to Pho92-dependent degradation. The results of the present study indicate that Pho92 regulates Pho4 expression at the post-transcriptional level via the regulation of mRNA stability. Taken together, Pho92 participates in cellular phosphate metabolism, specifically via the regulation of PHO4 mRNA stability by binding to the 3'-UTR in a phosphate-dependent manner.