title: Identification of a Mg2+-sensitive ORF in the 5'-leader of TRPM7 magnesium channel mRNA.
abstract: TRPM7 is an essential and ubiquitous channel-kinase regulating cellular influx of Mg2+. Although TRPM7 mRNA is highly abundant, very small amount of the protein is detected in cells, suggesting post-transcriptional regulation of trpm7 gene expression. We found that TRPM7 mRNA 5'-leader contains two evolutionarily conserved upstream open reading frames that act together to drastically inhibit translation of the TRPM7 reading frame at high magnesium levels and ensure its optimal translation at low magnesium levels, when the activity of the channel-kinase is most required. The study provides the first example of magnesium channel synthesis being controlled by Mg2+ in higher eukaryotes.
authors.affiliation: Department of Cellular and Molecular Pharmacology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
authors.forename: Inna A
authors.initials: IA
authors.lastname: Nikonorova
authors.affiliation: Department of Cellular and Molecular Pharmacology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Kornakov
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119992, Russia.
authors.forename: Sergey E
authors.initials: SE
authors.lastname: Dmitriev
authors.affiliation: Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
authors.forename: Konstantin S
authors.initials: KS
authors.lastname: Vassilenko
authors.affiliation: Department of Cellular and Molecular Pharmacology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA ryazanag@rwjms.rutgers.edu.
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Ryazanov
mesh_terms: D020121:5' Untranslated Regions; D001483:Base Sequence; D017124:Conserved Sequence; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008274:Magnesium / Q000494:pharmacology*; D016366:Open Reading Frames; D014176:Protein Biosynthesis / Q000187:drug effects; D050053:TRPM Cation Channels / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D050053:TRPM Cation Channels; C421903:Trpm7 protein, mouse; D008274:Magnesium