CELL-SIZE REGULATION, A MECHANISM THAT CONTROLS CELLULAR RNA ACCUMULATION - CONSEQUENCES ON REGULATION OF THE UBIQUITOUS TRANSCRIPTION FACTORS OCT1 AND NF-Y, AND THE LIVER-ENRICHED TRANSCRIPTION FACTOR DBP

Cell sizes can differ vastly between cell types in individual metazoan organisms. In rat liver, spleen, and thymus, differences in average c ell size roughly reflect differences in RNA:DNA ratios. For example, h epatocytes were found to have a cytoplasmic:nuclear volume ratio and a n RNA:DNA ratio which were 34- and 21-fold higher, respectively, than those in thymocytes. RNA synthesis per DNA-equivalent in the hepatocyt es was 25-fold greater than that in thymocytes, suggesting that differ ences in overall transcriptional activity, not differences in overall RNA stability, were primarily responsible for determining cellular RNA :DNA ratios. The mechanisms determining the capacity of large cells to synthesize and accumulate more ubiquitous cytoplasmic macromolecules, such as ribosomes, than smaller cells is entitled ''cell size regulat ion.'' Cell size regulation may have important consequences on the tis sue distribution of transcription factors. Thus, in liver, lung, kidne y: spleen, and brain, cellular levels of the mRNA encoding the leucine zip-per protein DBP correlate closely to cellular RNA:DNA ratios. Our results suggest that DBP mRNA levels, like rRNA levels, are transcrip tionally determined. Thus the dbp gene, like the ribosomal genes, may be subject to cell size regulation. As a consequence, nuclei from live r, a tissue with a very large average cell size, accumulated higher le vels of DBP protein than nuclei from Small-celled tissues, such as spl een or lung. In contrast to DBP, the ubiquitous transcription factors Oct1 and NF-Y escaped cell size control. Nuclei from most tissues cont ained similar amounts of these factors irrespective of cell size. Like wise, tissues with large or small average cell sizes contained similar levels of the mRNAs encoding Oct1 or NF-Ya, one of the subunits of th e heteromeric CCAAT-binding factor NF-Y, per DNA-equivalent. Interesti ngly, mRNA encoding NF-Yb, another subunit of NF-Y, was subject to cel l size regulation. Our results suggest that NF-Yb, protein escapes cel l size regulation at a posttranslational level.