Identification of cellular proteins enhancing activities of internal ribosomal entry sites by competition with oligodeoxynucleotides

Nucleic Acids Res. 2004 Feb 23;32(4):1308-17. doi: 10.1093/nar/gkh300. Print 2004.

Abstract

The translation of numerous eukaryotic mRNAs is mediated by internal ribosomal entry sites (IRESs). IRES-dependent translation requires both canonical translation initiation factors and IRES-specific trans-acting factors (ITAFs). Here we report a strategy to identify and characterize ITAFs required for IRES-dependent translation. This process involves steps for identifying oligodeoxynucleotides affecting IRES-dependent translation, purifying proteins interacting with the inhibitory DNA, identifying the specific proteins with matrix-assisted laser desorption ionization/time-of-flight mass spectrometry, and confirming the roles of these proteins in IRES-dependent translation by depletion and repletion of proteins from an in vitro translation system. Using this strategy, we show that poly(rC)-binding proteins 1 and 2 enhance translation through polioviral and rhinoviral IRES elements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions*
  • Amino Acid Sequence
  • DNA-Binding Proteins / physiology
  • HeLa Cells
  • Heterogeneous-Nuclear Ribonucleoproteins / antagonists & inhibitors
  • Heterogeneous-Nuclear Ribonucleoproteins / chemistry
  • Heterogeneous-Nuclear Ribonucleoproteins / physiology
  • Humans
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides / chemistry
  • Oligodeoxyribonucleotides / metabolism
  • Oligodeoxyribonucleotides / pharmacology*
  • Poliovirus / genetics
  • Protein Biosynthesis* / drug effects
  • RNA-Binding Proteins / analysis*
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / metabolism
  • Rhinovirus / genetics
  • Ribosomes / chemistry
  • Ribosomes / genetics
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Transcription Factors / physiology

Substances

  • 5' Untranslated Regions
  • DNA-Binding Proteins
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Oligodeoxyribonucleotides
  • PCBP1 protein, human
  • RNA-Binding Proteins
  • Transcription Factors