Suppression of eukaryotic translation termination by selected RNAs.
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.
Carnes
J
J
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309-0347, USA.
Frolova
L
L
Zinnen
S
S
Drugeon
G
G
Phillippe
M
M
Justesen
J
J
Haenni
A L
AL
Leinwand
L
L
Kisselev
L L
LL
Yarus
M
M
D000818:Animals; D001483:Base Sequence; D002213:Capsid / Q000096:biosynthesis / Q000235:genetics; D002855:Chromatography, Thin Layer; D018388:Codon, Terminator / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D018716:Molecular Mimicry; D009690:Nucleic Acid Conformation; D010443:Peptide Chain Termination, Translational / Q000187:drug effects*; D010454:Peptide Termination Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012313:RNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D013698:Templates, Genetic; D013816:Thermodynamics; D029867:Xenopus Proteins; D014982:Xenopus laevis
D018388:Codon, Terminator; C489002:ETF1 protein, human; D010454:Peptide Termination Factors; D012333:RNA, Messenger; D012367:RNA, Viral; C489001:SUP45 protein, Xenopus; D029867:Xenopus Proteins; C087971:peptide-chain-release factor 3; D012313:RNA; D020558:GTP Phosphohydrolases