GROWTH-CONDITION-DEPENDENT REGULATION OF INSULIN-LIKE GROWTH-FACTOR-II MESSENGER-RNA STABILITY

Insulin-like growth factor II (IGF-II) is synthesized in many tissues, but the main site of production is the liver. In this paper we show t hat IGF-II mRNA levels are dependent on the growth conditions of the c ells. In Hep3B cells, serum deprivation leads to a marked increase in IGF-II mRNA levels. Serum stimulation of starved Hep3B cells induces a decrease in the amount of IGF-II mRNA, which is not caused by a chang e in promoter activity. IGF-II mRNAs are subject to endonucleolytic cl eavage, a process that requires two widely separated elements in the 3 ' untranslated region of the mRNA. Specific regions of these elements can form a stable stem structure which is involved in the formation of RNA-protein complexes. By employing electrophoretic mobility shift as says, two complexes have been identified in cytoplasmic extracts of He p3B cells. The formation of these complexes is related to the growth c onditions of the cells and is correlated with the regulation of IGF-II mRNA levels. Our data suggest that, depending on whether serum is pre sent or absent, a transition from one complex to the other occurs. A d ecrease in the IGF-II mRNA level is also observed when IGF-I or IGF-II is added to serum-deprived Hep3B cells, possibly providing a feedback mechanism for IGF-II production. The serum-induced degradation of IGF -II mRNAs does not require de novo protein synthesis, and is abolished by rapamycin, an inhibitor of p70 S6 kinase.