Effect of Onconase on double-stranded RNA in vitro.
Onconase is a cytotoxic ribonuclease which targets tumor cells in vivo and in vitro. To date, cellular tRNA appeared to be the major target for Onconase mediated cytotoxic activity. Most recently we demonstrated that Onconase can also cleave double-stranded RNA (dsRNA). Incubation of Onconase at 37 degrees C with GAPDH gene-dsRNA (approximately 440 bp long) and dsRNA ladder showed degradation of dsRNA into a spectrum of smaller dsRNA fragments. Moreover, incubation of dsRNA substrates at 40 degrees C under similar conditions markedly potentiated further cleavage of dsRNAs. The recently discovered double-stranded RNase activity of Onconase suggests another mechanism for inducing cell death/apoptosis in malignant phenotypes via the RNA interference mechanism involving siRNA and miRNA.
Saxena
Abha
A
Alfacell Corporation, Somerset, New Jersey 08873, USA.
Saxena
Shailendra K
SK
Shogen
Kuslima
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004722:Endoribonucleases / Q000378:metabolism; D020868:Gene Silencing; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D012260:Ribonucleases / Q000494:pharmacology*
D000970:Antineoplastic Agents; D035683:MicroRNAs; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D004722:Endoribonucleases; D012260:Ribonucleases; C044803:ds RNase; C058703:ranpirnase