Transcriptional control of the endogenous MYC protooncogene by antisense RNA.
Transcriptional control of the endogenous MYC protooncogene by antisense RNA.
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反义RNA对内源性MYC原癌基因的转录控制。
DOI：
10.1073/pnas.84.21.7363
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发表时间：
1987
影响因子：
11.1
通讯作者：
Fumio Imamoto
中科院分区：
文献类型：
--
作者：
Kazushige Yokoyama;Fumio Imamoto
通过原生质体融合将携带反义人MYC DNA和大肠杆菌黄嘌呤/鸟嘌呤磷酸化核糖转移酶（Ecogpt）基因的质粒导入人早幼粒细胞白血病HL-60细胞系。在超过6个月的时间里，通过选择对越来越高水平的霉酚酸具有抗性的细胞，获得了反义MYC RNA的高水平表达。与亲代HL-60细胞相比，产生高水平反义MYC RNA的克隆中MYC蛋白的组成量减少了70%。在翻译水平和转录水平均观察到对MYC表达的抑制作用，这表明反义RNA可以调节MYC基因的转录。MYC先导序列的Pst I-Pvu II片段（920个碱基对）是该反义RNA的主要转录靶点。通过反义RNA抑制内源性MYC基因表达，降低细胞增殖，触发单核细胞分化。
A plasmid carrying antisense human MYC DNA and the gene encoding Escherichia coli xanthine/guanine phosphoribosyltransferase (Ecogpt) was introduced into human promyelocytic leukemia cell line HL-60 by protoplast fusion. High-level expression of antisense MYC RNA was obtained by selecting cells resistant to progressively higher levels of mycophenolic acid over a period of greater than 6 months. The constitutive production of MYC protein in clones producing high levels of antisense MYC RNA was reduced by 70% compared to parental HL-60 cells. Inhibition of MYC expression was observed not only at the translational but also at the transcriptional level, implying that antisense RNA can regulate transcription of the MYC gene. The Pst I-Pvu II fragment (920 base pairs) of the MYC leader sequence is the primary transcriptional target of the antisense RNA. The suppression of endogenous MYC gene expression by antisense RNA decreases cell proliferation and triggers monocytic differentiation.