Zinc inhibits turnover of labile mRNAs in intact cells

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Abstract
For immediate early genes such as the c-fos proto-oncogene, mRNA breakdown is very rapid and is largely responsible for the transient nature of mRNA accumulation after transcription is stimulated. We found that in several types of cultured cells and in mice, Zn++ caused marked accumulation of c-fos mRNA and that of another labile mRNA, that encoding the tristetraprolin (TTP) protein. Exposure of TK-L cells to 100 μM ZnSO4 caused an increase of c-fos and TTP mRNA levels within 1 h that reached peak levels in 4–8 h and remained constant to 12 h. Increases in fos protein accumulation were also noted. When the cells were exposed to Zn++ for 4 h and then exposed to actinomycin D, both c-fos and TTP mRNA levels remained constant for up to 10 h, indicating that Zn++ was preventing the breakdown of both c-fos and TTP mRNA. Also, 100 μM ZnSO4 inhibited protein synthesis in TK-L cells, suggesting that the effect on mRNA accumulation