Dicer is regulated by cellular stresses and interferons.
The generation of microRNAs is dependent on the RNase III enzyme Dicer, the levels of which vary in different normal cells and in disease states. We demonstrate that Dicer protein expression in JAR trophoblast cells, and several other cell types, was inhibited by multiple stresses including reactive oxygen species, phorbol esters and the Ras oncogene. Additionally, double-stranded RNA and Type I interferons repress Dicer protein in contrast to IFN-gamma which induces Dicer. The effects of stresses and interferons are primarily post-transcriptional. The findings suggest that Dicer is a stress response component and identifies interferons as potentially important regulators of Dicer expression.
Wiesen
Jennifer L
JL
Roswell Park Cancer Institute, Laboratory of Molecular Medicine, Department of Immunology, Elm & Carlton Streets, Buffalo, NY 14263, United States.
Tomasi
Thomas B
TB
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007370:Interferon Type I / Q000494:pharmacology / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D043244:Ribonuclease III / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014327:Trophoblasts / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007370:Interferon Type I; D035683:MicroRNAs; D010703:Phorbol Esters; D017382:Reactive Oxygen Species; C012589:trichostatin A; D007371:Interferon-gamma; D043244:Ribonuclease III; D018631:ras Proteins; D011070:Poly I-C