Regulation of the Relative Abundances of mRNAs in Hepatoma and Liver

Abstract

Comparison of the polysomal poly(A)+ RNAs of normal rat liver and hepatoma (HTC) cells have shown that, while few sequences are specific to either hepatocytes or hepatoma cells, some of the abundant liver mRNAs (perhaps 20% by weight) are much rarer in the polysomal RNA from HTC cells. In contrast, these mRNA sequences are at quite similar abundances in nuclear poly(A)+ RNA from hepatocytes and hepatoma cells. The use of cloned cDNAs to measure the relative abundances of individual liver mRNA sequences in hepatocytes and HTC cells has shown that these changes occur in both directions, and indicated that post-transcriptional modulations, which are cell-type-specific and sequence-specific, play a significant role in establishing steady-state levels of polysomal poly(A)+ mRNAs. To investigate post-transcriptional regulation of mRNA abundance, a cell-free system consisting of isolated HTC-cell nuclei has been developed. This system supports the in vitro processing and/or transport of rRNA and a complex mixture of poly(A)+ RNA sequences which resembles polysomal poly(A)+ RNA from HTC cells. The pattern of relative abundances of the sequences in released poly(A)+ RNA is intermediate between that of polysomal and nuclear poly(A)+ RNAs, and indicates that some degree of sequence-specific selection of processing and/or transport is maintained in isolated nuclei. Sequence-specific selection of individual poly(A)+ RNA sequences in vitro has been detected with cloned cDNAs.