Actinomycin prevents the destabilization of neurofilament mRNA in primary sensory neurons.
The levels of light, mid-sized, and heavy neurofilament (NF) mRNAs were compared to that of beta-actin mRNA in primary dissociated cultures of adult rat dorsal root ganglia (DRG). Decreases in the levels of all three NF mRNAs occur after 24 h in culture, mimicking the down-regulation of NF mRNAs in axotomized DRG neurons. The loss of NF mRNAs in DRG cultures is prevented by actinomycin and, to a lesser extent, by cycloheximide. Based on decay curves in actinomycin-treated cultures, the half-lives of NF mRNAs are at least 4 days in DRG neurons, but < 24 h in PC12 cells. Our data support the view that NF mRNAs are stabilized in DRG neurons and that stabilization prevents destabilization by a transcription-dependent process. We further propose that putative stabilizing factor(s) are able to prevent degradation of NF transcripts in intact neurons, but not in axotomized or cultured neurons.
D000546:Amanitins / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000502:physiology; D007382:Intermediate Filaments / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D007700:Kinetics; D016900:Neurofilament Proteins / Q000096:biosynthesis / Q000235:genetics*; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects
D000546:Amanitins; D016900:Neurofilament Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin