Aminoglycosides and other factors promoting stop codon readthrough in human cells.
Enhanced stop codon readthrough is a potential treatment strategy for diseases caused by nonsense mutations. Here, we compare readthrough levels induced by three types of factors: aminoglycoside antibiotics, suppressor tRNAs, and factors decreasing translation termination efficiency. We show that the highest levels of readthrough were obtained by prolonged treatment with aminoglycosides and suppressor tRNAs, whereas prolonged depletion of release factors induced only a moderate increase in readthrough. We discuss the benefits and inconvenients of the three types of factors for their use in the therapy of diseases caused by premature stop codons.
Diop
Dialo
D
Unité de biochimie cellulaire, université Pierre-et-Marie-Curie, Paris-6, UMR 7098 CNRS, 9, quai Saint-Bernard, 75252 Paris cedex 05, France.
Chauvin
Céline
C
Jean-Jean
Olivier
O
D000617:Aminoglycosides / Q000494:pharmacology*; D002460:Cell Line; D002701:Chloramphenicol / Q000494:pharmacology; D003062:Codon / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007668:Kidney; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering
D000617:Aminoglycosides; D003062:Codon; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D002701:Chloramphenicol