Suppression of eukaryotic translation termination by selected RNAs.

  1. J Carnes,
  2. L Frolova,
  3. S Zinnen,
  4. G Drugeon,
  5. M Phillippe,
  6. J Justesen,
  7. A L Haenni,
  8. L Leinwand,
  9. L L Kisselev, and
  10. M Yarus
  1. Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309-0347, USA.

Abstract

Using selection-amplification, we have isolated RNAs with affinity for translation termination factors eRF1 and eRF1.eRF3 complex. Individual RNAs not only bind, but inhibit eRF1-mediated release of a model nascent chain from eukaryotic ribosomes. There is also significant but weaker inhibition of eRF1-stimulated eRF3 GTPase and eRF3 stimulation of eRF1 release activity. These latter selected RNAs therefore hinder eRF1.eRF3 interactions. Finally, four RNA inhibitors of release suppress a UAG stop codon in mammalian extracts dependent for termination on eRF1 from several metazoan species. These RNAs are therefore new specific inhibitors for the analysis of eukaryotic termination, and potentially a new class of omnipotent termination suppressors with possible therapeutic significance.

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