An early effect of retinoic acid: cloning of an mRNA (Era-1) exhibiting rapid and protein synthesis-independent induction during teratocarcinoma stem cell differentiation.
An early effect of retinoic acid: cloning of an mRNA (Era-1) exhibiting rapid and protein synthesis-independent induction during teratocarcinoma stem cell differentiation.
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DOI：
10.1073/pnas.85.2.329
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发表时间：
1988
影响因子：
11.1
通讯作者：
G. Larosa;L. Gudas
中科院分区：
文献类型：
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作者：
G. Larosa;L. Gudas
维生素A及其衍生物（类维生素A）对许多细胞类型的增殖和分化具有深远的影响。然而，维甲酸发挥这些作用的分子机制尚不清楚。培养的小鼠F9畸胎瘤干细胞，其中分化成非致瘤性内胚层细胞响应于视黄酸（RA），已被用于确定基因调节RA。用富含RA快速诱导序列的cDNA探针筛选了用RA处理8小时的F9细胞合成的cDNA文库，并鉴定了表现出RA主要靶点特征的基因。这个基因，早期视黄酸-1（Era-1），编码一个2.2- 2.4-腺苷酸酶多聚腺苷酸化的RNA; Era-1 mRNA的水平迅速和短暂增加高达35倍，这取决于外源性RA的浓度。Era-1 mRNA的增加依赖于外源性RA的持续存在。RA相关的Era-1 mRNA的增加甚至在蛋白质合成抑制剂的存在下也可以看到，但是RNA合成抑制剂如放线菌素D可以阻止这种增加。F9细胞中Era-1 mRNA稳态水平的增加是视黄酸对该分化系统中基因表达的非常早期的影响。
Vitamin A and its derivatives (retinoids) exhibit profound effects on the proliferation and differentiation of many cell types. However, the molecular mechanism by which retinoids exert these effects is unknown. Cultured murine F9 teratocarcinoma stem cells, which differentiate into nontumorigenic endoderm cells in response to retinoic acid (RA), have been used to identify genes regulated by RA. A cDNA library synthesized from F9 cells treated with RA for 8 hr has been screened with a cDNA probe enriched for sequences rapidly induced by RA, and a gene that exhibits the characteristics of a primary target for RA has been identified. This gene, early retinoic acid-1 (Era-1), encodes a 2.2- to 2.4-kilobase polyadenylylated RNA; the level of Era-1 mRNA rapidly and transiently increases up to 35-fold, depending on the concentration of exogenous RA. The increase in Era-1 mRNA is dependent on the continuous presence of exogenous RA. The RA-associated increase in Era-1 mRNA is seen even in the presence of protein synthesis inhibitors, but the increase is prevented by inhibitors of RNA synthesis such as actinomycin D. This increase in the steady-state level of Era-1 mRNA in F9 cells is a very early effect of retinoic acid on gene expression in this differentiation system.