Iron regulatory protein prevents binding of the 43S translation pre-initiation complex to ferritin and eALAS mRNAs

EMBO J. 1994 Aug 15;13(16):3882-91.

Abstract

Translation of ferritin and erythroid 5-aminolevulinate synthase (eALAS) mRNAs is regulated by iron via mRNA-protein interactions between iron-responsive elements (IREs) and iron regulatory protein (IRP). In iron-depleted cells, IRP binds to single IREs located in the 5' untranslated regions of ferritin and eALAS mRNAs and represses translation initiation. The molecular mechanism underlying this translational repression was investigated using reconstituted, IRE-IRP-regulated, cell-free translation systems. The IRE-IRP interaction is shown to prevent the association of the 43S translation pre-initiation complex (including the small ribosomal subunit) with the mRNA. Studies with the spliceosomal protein U1A and mRNAs which harbour specific binding sites for this protein in place of an IRE furthermore reveal that the 5' termini of mRNAs are generally sensitive to repressor protein-mediated inhibition of 43S pre-initiation complex binding.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Aminolevulinate Synthetase / genetics*
  • Animals
  • Cell-Free System
  • Chloramphenicol O-Acetyltransferase / genetics
  • Ferritins / genetics*
  • Genes, Reporter
  • Iron-Regulatory Proteins
  • Models, Genetic
  • Peptide Chain Initiation, Translational*
  • Protein Binding
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Rabbits
  • Regulatory Sequences, Nucleic Acid
  • Repressor Proteins / metabolism
  • Reticulocytes
  • Ribonucleoprotein, U1 Small Nuclear / metabolism
  • Ribosomes / metabolism

Substances

  • Iron-Regulatory Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Repressor Proteins
  • Ribonucleoprotein, U1 Small Nuclear
  • U1A protein
  • Ferritins
  • Chloramphenicol O-Acetyltransferase
  • 5-Aminolevulinate Synthetase