Coordinated Remodeling of Cellular Metabolism During Iron Deficiency Through Targeted mRNA Degradation

Cell. 2005 Jan 14;120(1):99-110. doi: 10.1016/j.cell.2004.11.032.

Abstract

Iron (Fe) is an essential micronutrient for virtually all organisms and serves as a cofactor for a wide variety of vital cellular processes. Although Fe deficiency is the primary nutritional disorder in the world, cellular responses to Fe deprivation are poorly understood. We have discovered a posttranscriptional regulatory process controlled by Fe deficiency, which coordinately drives widespread metabolic reprogramming. We demonstrate that, in response to Fe deficiency, the Saccharomyces cerevisiae Cth2 protein specifically downregulates mRNAs encoding proteins that participate in many Fe-dependent processes. mRNA turnover requires the binding of Cth2, an RNA binding protein conserved in plants and mammals, to specific AU-rich elements in the 3' untranslated region of mRNAs targeted for degradation. These studies elucidate coordinated global metabolic reprogramming in response to Fe deficiency and identify a mechanism for achieving this by targeting specific mRNA molecules for degradation, thereby facilitating the utilization of limited cellular Fe levels.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • DNA-Binding Proteins / metabolism
  • Down-Regulation / physiology
  • Gene Expression Regulation, Fungal / genetics
  • Iron / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Plasmids / genetics
  • RNA Processing, Post-Transcriptional / physiology*
  • RNA, Messenger / metabolism*
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription, Genetic
  • Tristetraprolin

Substances

  • DNA-Binding Proteins
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • TIS11 protein, S cerevisiae
  • Tristetraprolin
  • Iron