Sodium butyrate modifies the stabilizing complexes of tyrosine hydroxylase mRNA.
Multiple mechanisms regulate the expression of the tyrosine hydroxylase (Th) gene, which encodes the rate-limiting enzyme in the biosynthesis of catecholamines. Sodium butyrate (SOB), a physiological histone deacetylase (HDAC) inhibitor, was reported to stimulate the Th gene promoter activity in reporter gene assays. However, the expression of the endogenous Th gene in PC12 cells was reported to be either stimulated or inhibited by SOB. Here, we report that SOB and other HDAC inhibitors drastically (up to 90%) and reversibly decrease the level of TH mRNA in PC12 cells. We also show that SOB does not influence the transcription initiation rate of the Th gene but perturbs the formation of protein-RNA complexes at the 3'UTR of the gene. Our results suggest that SOB inhibits the expression of the Th gene by destabilizing TH mRNAs.
Arányi
T
T
CNRS UMR 7091 - Université Pierre et Marie Curie (Paris 6), Hôpital de la Pitié Salpêtrière (Bâtiment CERVI), 83 Bd de l'hôpital, 75013 Paris, France.
Sarkis
C
C
Berrard
S
S
Sardin
K
K
Siron
V
V
Khalfallah
O
O
Mallet
J
J
D000818:Animals; D002087:Butyrates / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004795:Enzyme Stability; D056572:Histone Deacetylase Inhibitors; D016716:PC12 Cells; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000378:metabolism*
D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase