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 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.
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DOI：
10.1083/jcb.128.4.467
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发表时间：
1995-02
期刊：
影响因子：
--
通讯作者：
Schibler U
中科院分区：
文献类型：
--
作者：
Schmidt EE;Schibler U
在个体后生动物有机体中，细胞大小在细胞类型之间可以有很大差异。在大鼠肝脏、脾脏和胸腺中，平均细胞大小的差异大致反映了RNA：DNA比例的差异。例如，发现肝细胞的细胞质：细胞核体积比和RNA：DNA比分别比胸腺细胞高34倍和21倍。在肝细胞中，每DNA当量的RNA合成是胸腺细胞的25倍，这表明总体转录活性的差异，而不是总体RNA稳定性的差异，是决定细胞RNA：DNA比例的主要原因。决定大细胞比小细胞合成和积累更多普遍存在的细胞质大分子（如核糖体）的能力的机制被称为“细胞大小调节”。“细胞大小调节可能对转录因子的组织分布产生重要影响。因此，在肝、肺、肾、脾和脑中，编码亮氨酸拉链蛋白DBP的mRNA的细胞水平与细胞RNA：DNA比率密切相关。我们的研究结果表明，DBP mRNA水平，像rRNA水平，转录决定。因此，dbp基因，像核糖体基因一样，可能受到细胞大小的调节。因此，来自肝脏（具有非常大的平均细胞尺寸的组织）的细胞核比来自小细胞组织（例如脾或肺）的细胞核积累更高水平的DBP蛋白。与DBP相反，普遍存在的转录因子Oct 1和NF-Y逃脱了细胞大小的控制。无论细胞大小，大多数组织的细胞核含有类似数量的这些因子。同样，平均细胞大小不同的组织中，每一个DNA当量的Oct 1或NF-Ya（异聚体CCAAT结合因子NF-Y的亚基之一）的mRNA编码水平相似。有趣的是，编码NF-Yb（NF-Y的另一个亚基）的mRNA受到细胞大小调节。我们的研究结果表明，NF-Yb蛋白逃逸细胞大小的调控在翻译后水平。
Cell sizes can differ vastly between cell types in individual metazoan organisms. In rat liver, spleen, and thymus, differences in average cell size roughly reflect differences in RNA:DNA ratios. For example, hepatocytes were found to have a cytoplasmic:nuclear volume ratio and an RNA:DNA ratio which were 34- and 21-fold higher, respectively, than those in thymocytes. RNA synthesis per DNA-equivalent in the hepatocytes was 25-fold greater than that in thymocytes, suggesting that differences 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 regulation." Cell size regulation may have important consequences on the tissue distribution of transcription factors. Thus, in liver, lung, kidney, spleen, and brain, cellular levels of the mRNA encoding the leucine zipper protein DBP correlate closely to cellular RNA:DNA ratios. Our results suggest that DBP mRNA levels, like rRNA levels, are transcriptionally determined. Thus the dbp gene, like the ribosomal genes, may be subject to cell size regulation. As a consequence, nuclei from liver, a tissue with a very large average cell size, accumulated higher levels of DBP protein than nuclei from small-celled tissues, such as spleen or lung. In contrast to DBP, the ubiquitous transcription factors Oct1 and NF-Y escaped cell size control. Nuclei from most tissues contained similar amounts of these factors irrespective of cell size. Likewise, tissues with large or small average cell sizes contained similar levels of the mRNAs encoding Oct1 or NF-Ya, one of the subunits of the heteromeric CCAAT-binding factor NF-Y, per DNA-equivalent. Interestingly, mRNA encoding NF-Yb, another subunit of NF-Y, was subject to cell size regulation. Our results suggest that NF-Yb protein escapes cell size regulation at a posttranslational level.