Accumulation of rare and moderately abundant mRNAs in mouse L-cells is mainly post-transcriptionally regulated.

We have isolated ten complementary DNA recombinant plasmids, five for moderately abundant and five for rare L-cell mRNAs. The plasmids pLc1 to pLc5 contain inserts homologous to mRNAs that accumulate 220 to 640 copies per L-cell, while the plasmids pLc6 to pLc10 are complementary to rare mRNAs that accumulate 5 to 76 copies per L-cell. The cDNA plasmids pLc1 to pLc10 hybridize to cytoplasmic polyadenylated RNAs from several tissues. Thus it appears likely that the ten investigated mRNAs are coding for "housekeeping" functions. The relative transcription rates of the genes Lc1 to Lc10 were estimated by run-off transcription experiments in isolated L-cell nuclei. The results indicate that the transcription rates of genes that specify the moderately abundant mRNAs, Lc1 to Lc5, are not significantly higher than the genes specifying the rare mRNAs, Lc6 to Lc10. Thus the steady-state concentrations of the ten mRNAs investigated are modulated mainly at the post-transcriptional level. Kinetic labelling experiments confirm this conclusion and indicate that differential mRNA stability in the cytoplasm is largely responsible for the variation in accumulation of Lc1 to Lc10 mRNAs. Since housekeeping genes comprise the large majority of active genes, post-transcriptional regulation may well be the prevalent control in eucaryotic cells to determine the individual mRNA levels.