Open AccessMagnesium-sensitive upstream ORF controls PRL phosphatase expression to mediate energy metabolism
Author(s) -
Serge Hardy,
Elie Kostantin,
Shan Jin Wang,
Tzvetena Hristova,
Gabriela Galicia-Vázquez,
Pavel V. Baranov,
Jerry Pelletier,
Michel L. Tremblay
Publication year - 2019
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1815361116
Subject(s) - magnesium , microbiology and biotechnology , phosphatase , intracellular , biology , translation (biology) , mechanism (biology) , messenger rna , ampk , repressor , biochemistry , chemistry , phosphorylation , gene expression , protein kinase a , gene , philosophy , organic chemistry , epistemology
Significance The phosphatases of regenerative liver (PRL) have been shown to interact with the CNNM magnesium transport regulators. Through this protein complex, PRL controls the levels of intracellular magnesium. Our study uncovers a remarkable posttranscriptional feedback mechanism by which magnesium controls PRL expression in mammalian cells. Here we show that regulation of PRL mRNA translation by magnesium depends on a 5′UTR-located upstream ORF, which is conserved among all vertebrates, proposing an evolutionary molecular mechanism of action by a divalent ion. This magnesium-sensing mechanism, which also involves the key metabolic sensor AMPK, is thus central to maintain cellular homeostasis in mammalian cells.
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