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Suppression of eukaryotic translation termination by selected RNAs

Published online by Cambridge University Press:  08 December 2000

JASON CARNES ,
LUDMILA FROLOVA ,
SHAWN ZINNEN ,
GABRIÈLE DRUGEON ,
MICHEL PHILLIPPE ,
JUST JUSTESEN ,
ANNE-LISE HAENNI ,
LESLIE LEINWAND ,
LEV L. KISSELEV  and
MICHAEL YARUS
JASON CARNES
Affiliation:
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309-0347, USA
LUDMILA FROLOVA
Affiliation:
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 117984 Moscow, Russia
SHAWN ZINNEN
Affiliation:
Ribozyme Pharmaceuticals, Inc., Boulder, Colorado 80301-5411, USA
GABRIÈLE DRUGEON
Affiliation:
Institut Jacques Monod, 75251 Paris Cedex 05, France
MICHEL PHILLIPPE
Affiliation:
Département de Biologie Génétique du Développement, Centre National de la Recherche Scientifique Unité Propre de Recherche 41, 35043 Rennes Cedex, France
JUST JUSTESEN
Affiliation:
Department of Molecular and Structural Biology, University of Aarhus, DK-8000 Aarhus C, Denmark
ANNE-LISE HAENNI
Affiliation:
Institut Jacques Monod, 75251 Paris Cedex 05, France
LESLIE LEINWAND
Affiliation:
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309-0347, USA
LEV L. KISSELEV
Affiliation:
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 117984 Moscow, Russia
MICHAEL YARUS
Affiliation:
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309-0347, USA
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Abstract

Using selection-amplification, we have isolated RNAs with affinity for translation termination factors eRF1 and eRF1[bull ]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[bull ]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.

Keywords

aptamerhumaninhibitorrelease factorstop codon

Information

Type
Research Article
Information
RNA , Volume 6 , Issue 10 , October 2000 , pp. 1468 - 1479
Copyright
2000 RNA Society

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