title: A novel protein, Pho92, has a conserved YTH domain and regulates phosphate metabolism by decreasing the mRNA stability of PHO4 in Saccharomyces cerevisiae.
abstract: 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 Δpho92 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 Δpho92 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.
authors.affiliation: *School of Life Sciences and Biotechnology, Korea University, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea.
authors.forename: Hyun-Jun
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: *School of Life Sciences and Biotechnology, Korea University, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea.
authors.forename: Sook-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.affiliation: †Department of Molecular Biology, Plant Engineering Research Institute (PERI), Sejong University, Seoul 143-747, Republic of Korea.
authors.forename: Kyung-Nam
authors.initials: KN
authors.lastname: Kim
authors.affiliation: *School of Life Sciences and Biotechnology, Korea University, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea.
authors.forename: In-Joon
authors.initials: IJ
authors.lastname: Baek
authors.affiliation: *School of Life Sciences and Biotechnology, Korea University, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea.
authors.forename: Miwha
authors.initials: M
authors.lastname: Chang
authors.affiliation: *School of Life Sciences and Biotechnology, Korea University, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea.
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Kang
authors.affiliation: *School of Life Sciences and Biotechnology, Korea University, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea.
authors.forename: Yong-Sung
authors.initials: YS
authors.lastname: Park
authors.affiliation: *School of Life Sciences and Biotechnology, Korea University, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea.
authors.forename: Cheol-Won
authors.initials: CW
authors.lastname: Yun
mesh_terms: D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D059365:Nonsense Mediated mRNA Decay; D028061:Phosphate Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D000072260:RNA Splicing Factors; D020871:RNA Stability; D012329:RNA, Bacterial / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012260:Ribonucleases / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D039221:mRNA Cleavage and Polyadenylation Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C060292:PHO4 protein, S cerevisiae; C587019:Pho92 protein, S cerevisiae; D028061:Phosphate Transport Proteins; D010710:Phosphates; D000072260:RNA Splicing Factors; D012329:RNA, Bacterial; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C450580:YTH1 protein, S cerevisiae; C490769:YTHDC1 protein, human; C585900:YTHDF2 protein, human; D039221:mRNA Cleavage and Polyadenylation Factors; D012260:Ribonucleases; C079009:POP2 protein, S cerevisiae