Identification of a Mg2+-sensitive ORF in the 5'-leader of TRPM7 magnesium channel mRNA

Nucleic Acids Res. 2014 Nov 10;42(20):12779-88. doi: 10.1093/nar/gku951. Epub 2014 Oct 17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions*
  • Base Sequence
  • Conserved Sequence
  • Gene Expression Regulation*
  • HEK293 Cells
  • Humans
  • Magnesium / pharmacology*
  • Open Reading Frames*
  • Protein Biosynthesis* / drug effects
  • TRPM Cation Channels / genetics*

Substances

  • 5' Untranslated Regions
  • TRPM Cation Channels
  • Trpm7 protein, mouse
  • Magnesium