Regulation of P120 mRNA levels during lymphocyte stimulation: evidence that the P120 gene shares properties with early and late genes.
P120 is a growth-regulated nucleolar protein, the expression of which is required for G1- to S-phase transition in lymphocytes. P120 appears to be involved in ribosomal biogenesis presumptively through its putative role as a rRNA methyltransferase. To better understand the role of P120 in cell cycle progression, we examined the regulation of the P120 gene in resting lymphocytes and in mitogen-stimulated lymphocytes as they progress from G1-phase toward S-phase. P120 mRNA was detected after the immediate early gene c-fos and persisted as the cells approached S-phase. A decrease in P120 mRNA coincided with the expression of histone H3 mRNA. The level of P120 mRNA increased as cells proceeded through G1-phase, and this increase was attributed to a more than threefold increase in the P120 transcription rate and an increase in P120 mRNA stability. The P120 gene is transcribed in resting lymphocytes, although the steady-state level of P120 is small or nonexistent. P120 mRNA accumulates in resting cells in the presence of the protein synthesis inhibitor cycloheximide. Furthermore, the steady-state level of P120 mRNA increases in the presence of cycloheximide after PHA-stimulation; this level does not increase in cells not treated with this protein synthesis inhibitor. The presence of cycloheximide increases both the transcription rate of the P120 gene and the stability of P120 mRNA. These studies indicate that P120 expression is cell cycle regulated in a complex manner and that the P120 gene has properties of both early and late genes. This time ordered regulation for P120 expression may represent a necessary step for the cell cycle associated increase in ribosomal biogenesis that is required for G1-to S-phase transition.
Wilson
A
A
University of Kentucky Medial Center, Department of Surgery, Lexington 40536-0084, USA.
Freeman
J W
JW
D002453:Cell Cycle / Q000235:genetics*; D016193:G1 Phase / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D006207:Half-Life; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D008934:Mitogens / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D016196:S Phase / Q000235:genetics; D013268:Stimulation, Chemical; D014158:Transcription, Genetic; D015854:Up-Regulation; D012359:tRNA Methyltransferases
D008934:Mitogens; D009687:Nuclear Proteins; D012333:RNA, Messenger; C065028:NOP2 protein, human; D012359:tRNA Methyltransferases