Control of mRNA decay by heat shock-ubiquitin-proteasome pathway

Science. 1999 Apr 16;284(5413):499-502. doi: 10.1126/science.284.5413.499.

Abstract

Cytokine and proto-oncogene messenger RNAs (mRNAs) are rapidly degraded through AU-rich elements in the 3' untranslated region. Rapid decay involves AU-rich binding protein AUF1, which complexes with heat shock proteins hsc70-hsp70, translation initiation factor eIF4G, and poly(A) binding protein. AU-rich mRNA decay is associated with displacement of eIF4G from AUF1, ubiquitination of AUF1, and degradation of AUF1 by proteasomes. Induction of hsp70 by heat shock, down-regulation of the ubiquitin-proteasome network, or inactivation of ubiquitinating enzyme E1 all result in hsp70 sequestration of AUF1 in the perinucleus-nucleus, and all three processes block decay of AU-rich mRNAs and AUF1 protein. These results link the rapid degradation of cytokine mRNAs to the ubiquitin-proteasome pathway.

Publication types

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

MeSH terms

  • 3' Untranslated Regions
  • Carrier Proteins / metabolism
  • Cell Nucleus / metabolism
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Cytoplasm / metabolism
  • Eukaryotic Initiation Factor-4G
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins / metabolism*
  • HeLa Cells
  • Heat-Shock Response*
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D*
  • Humans
  • Leupeptins / pharmacology
  • Multienzyme Complexes / metabolism*
  • Peptide Initiation Factors / metabolism
  • Poly(A)-Binding Proteins
  • Proteasome Endopeptidase Complex
  • Protein Binding
  • Proto-Oncogene Mas
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Transfection
  • Ubiquitins / metabolism*

Substances

  • 3' Untranslated Regions
  • Carrier Proteins
  • Cysteine Proteinase Inhibitors
  • Eukaryotic Initiation Factor-4G
  • HNRNPD protein, human
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • HSPA8 protein, human
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D
  • Leupeptins
  • MAS1 protein, human
  • Multienzyme Complexes
  • Peptide Initiation Factors
  • Poly(A)-Binding Proteins
  • Proto-Oncogene Mas
  • RNA, Messenger
  • RNA-Binding Proteins
  • Ubiquitins
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde