Competitive binding of AUF1 and TIAR to MYC mRNA controls its translation

Nat Struct Mol Biol. 2007 Jun;14(6):511-8. doi: 10.1038/nsmb1249. Epub 2007 May 7.

Abstract

(A+U)-rich elements (AREs) within 3' untranslated regions are signals for rapid degradation of messenger RNAs encoding many oncoproteins and cytokines. The ARE-binding protein AUF1 contributes to their degradation. We identified MYC proto-oncogene mRNA as a cellular AUF1 target. Levels of MYC translation and cell proliferation were proportional to AUF1 abundance but inversely proportional to the abundance of the ARE-binding protein TIAR, a MYC translational suppressor. Both AUF1 and TIAR affected MYC translation via the ARE without affecting mRNA abundance. Altering association of one ARE-binding protein with MYC mRNA in vivo reciprocally affected mRNA association with the other protein. Finally, genetic experiments revealed that AUF1 and TIAR control proliferation by a MYC-dependent pathway. Together, these observations suggest a novel regulatory mechanism where tuning the ratios of AUF1 and TIAR bound to MYC mRNA permits dynamic control of MYC translation and cell proliferation.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Binding, Competitive / genetics*
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation
  • Genes, myc / genetics*
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D / metabolism*
  • Humans
  • Immunoprecipitation
  • Polyribosomes / genetics
  • Polyribosomes / metabolism
  • Protein Biosynthesis / genetics*
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • HNRPD protein, human
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D
  • RNA, Messenger
  • RNA-Binding Proteins
  • TIAL1 protein, human