LOCUS UNLINKED TO ALPHA-FETOPROTEIN UNDER THE CONTROL OF THE MURINE RAF AND RIF GENES
LOCUS UNLINKED TO ALPHA-FETOPROTEIN UNDER THE CONTROL OF THE MURINE RAF AND RIF GENES
复制标题
DOI：
10.1073/pnas.81.17.5523
复制
发表时间：
1984-01-01
期刊：
影响因子：
--
通讯作者：
TILGHMAN, SM
中科院分区：
文献类型：
--
作者：
PACHNIS, V;BELAYEW, A;TILGHMAN, SM
小鼠中甲胎蛋白mRNA的水平由至少2个反式作用、非连锁基因raf和Rif决定。 raf确定成年小鼠中甲胎蛋白mRNA的基础水平，而Rif确定其在肝再生过程中的诱导程度。为了确定这些调节位点是否影响其他结构基因，在鼠胎肝c[互补]DNA文库中筛选了含有出生后减少的mRNA序列的克隆。一种这样的克隆被鉴定为 pH19，其 mRNA 显示受 raf 和 Rif 的控制。 H19 mRNA 的单拷贝基因位于 7 号染色体上，遗传杂交证实它与 raf 或 Rif 均无关。它编码2.5kb的mRNA，该mRNA在产生甲胎蛋白的组织中被鉴定：内脏内胚层、肝脏和胎儿肠道。新生儿肝脏中H19 mRNA的抑制发生在甲胎蛋白mRNA减少几天后，而在F9畸胎癌细胞分化为内脏内胚层期间两种mRNA的诱导是相同的。 H19 mRNA的组织特异性表达与甲胎蛋白的组织特异性表达不同，因为在不产生甲胎蛋白mRNA的心肌和骨骼肌中也检测到H19 mRNA。尽管出生后心肌中H19 mRNA水平下降至1/10至1/20，但成年后的基础水平不受raf的影响。这一观察表明 raf 基因是 mRNA 水平的组织特异性调节因子。
The levels of .alpha.-fetoprotein mRNA in mice are determined by at least 2 trans-acting, unlinked genes, raf and Rif. raf determines the basal levels of .alpha.-fetoprotein mRNA in adult mice, while Rif determines its degree of inducibility during liver regeneration. To determine whether these regulatory loci affect other structural genes, a murine fetal liver c[complementary]DNA library was screened for clones containing mRNA sequences that decrease after birth. One such clone, termed pH19, was identified, and its mRNA was shown to be under the control of both raf and Rif. The single-copy gene for H19 mRNA was localized to chromosome 7, and genetic crosses established that it was unlinked to either raf or Rif. It encodes a 2.5-kilobase mRNA that was identified in those tissues that produce .alpha.-fetoprotein: visceral endoderm, liver and fetal gut. The repression of H19 mRNA in neonatal liver occurs several days after the decrease in .alpha.-fetoprotein mRNA, whereas inductions of both mRNA during the differentiation of F9 teratocarcinoma cells into visceral endoderm were identical. The tissue-specific expression of H19 mRNA is different from that of .alpha.-fetoprotein in that H19 mRNA was detected also in both cardiac and skeletal muscle where no .alpha.-fetoprotein mRNA is produced. Despite the fact that the levels of H19 mRNA decline to 1/10th to 1/20th in cardiac muscle after birth, the adult basal levels are not under the influence of raf. This observation argues that the raf gene is a tissue-specific regulator of mRNA levels.