Relationship between nuclear ADP-ribosylation and RNA transcription in calf and human thyroid

Abstract

ADP-ribosylation is a posttranslational modification of proteins that has been related to many cellular events, such as DNA replication and repair, cell proliferation and differentiation. The present studies were performed in order to explore the possible relationship between nuclear protein ADP-ribosylation and RNA transcription in the thyroid gland. Inhibition of RNA transcription by alpha-amanitin and actinomycin D caused a decrease in ADP-ribosylation of 27 and 17%, respectively. Nicotinamide caused a dose-related inhibition of ADP-ribosylation, which was highest at 2 mM (around 90%). At this dose nicotinamide inhibited total RNA transcription by 46%, while the activity due to RNA polymerase II decreased by 50% and that related to RNA polymerases I+III dropped by 24%. These results suggest that inhibition of total nuclear protein ADP-ribosylation is accompanied by a parallel decrease in RNA transcription. Since our previous work has shown that TSH stimulates both nuclear ADP-ribosylation and RNA transcription it may be concluded that these activities follow parallel changes within the thyroid. When the same activities were assayed in normal human and in glands bearing follicular adenoma, RNA polymerase II was increased 4 fold in the latter group, without change in nuclear ADP-ribosylation. These results would suggest that a mechanism, distinct from ADP-ribosylation, may also be involved in the regulation of RNA transcription. This latter might be altered under this pathologic condition.