Ethanol stimulates apolipoprotein B mRNA editing in the absence of de novo RNA or protein synthesis.
Apolipoprotein B (apoB) mRNA editing involves a site-specific modification of cytidine to form uridine. The reaction is catalyzed in the nucleus by a multi-protein editosome. Rat hepatic editing is regulated during development, metabolically and in response to ethanol. Ethanol stimulated editing in hepatocytes within minutes of exposure. In the present study, we show that ethanol stimulated apoB mRNA synthesis and apoB mRNA editing. Significantly, the proportion of edited apoB mRNA also increased following ethanol treatment of transcription or translation arrested cells. These data suggested that ethanol could regulate editing activity using pre-existing editosomal proteins. In addition, the presence of a suppressor of apoB mRNA editing activity was suggested by the finding that inhibition of mRNA or protein synthesis alone was sufficient to increase the proportion of edited RNA. It is proposed that the level of editing activity observed in hepatocytes may be the end result of positive and negative regulatory proteins.
Giangreco
A
A
Department of Biochemistry and Biophysics, James P. Wilmot Cancer Center, University of Rochester, School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, New York 14623, USA.
Sowden
M P
MP
Mikityansky
I
I
Smith
H C
HC
D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004640:Emetine / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D017393:RNA Editing / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats
D001055:Apolipoproteins B; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D000431:Ethanol; D012313:RNA; D004640:Emetine