Normal developing rat brain expresses a platelet-derived growth factor B chain (c-sis) mRNA truncated at the 5′ end
Normal developing rat brain expresses a platelet-derived growth factor B chain (c-sis) mRNA truncated at the 5′ end
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DOI：
10.1038/sj.onc.1201679
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发表时间：
1998-03-26
期刊：
影响因子：
8
通讯作者：
Hazama, F
中科院分区：
文献类型：
--
作者：
Sasahara, M;Amano, S;Hazama, F
血小板衍生生长因子 B (PDGF-B/c-sis) mRNA 的 5' 非翻译序列 (5' UTS) 在进化过程中高度保留，并抑制下游编码序列的翻译。在本研究中，使用 Northern 分析，我们鉴定了在正常发育的大鼠大脑中表达的两种 PDGF-B/c-sis mRNA（3.5 kb 和 2.6 kb）。与 3.5 kb mRNA 的组成型表达相反，2.6 kb mRNA 的表达根据大脑发育的那些阶段显着增加，在这些阶段我们之前已经证明神经元中 PDGF-B/c-SIS 的免疫反应性增加（Sasahara 等人，1992）。通过PCR克隆和RNase保护测定，我们确定了大鼠PDGF-B/c-sis的完整序列，发现2.6 kb转录物是在5'端截短的3.5 kb信息的一种形式，并且主要的2.6 kb mRNA开始于信号肽上游15 nt，因此，这表明5' UTS的截短有助于表达 CNS 中的 PDGF-B/c-SIS 蛋白，仅在少数转化细胞和培养的脐静脉内皮细胞中报道了 PDGF-B/c-sis 转录物翻译抑制 5' UTS 的缺乏以及由此产生的有效蛋白质翻译。我们已将这一知识扩展到发育中的大鼠大脑，并表明类似的机制可以在体内非转化组织中广泛运作。
The 5' untranslated sequence (5' UTS) of platelet-derived growth factor B (PDGF-B/c-sis) mRNA is highly preserved through evolution, and inhibits translation of downstream coding sequences, In this study, using Northern analysis we identified two PDGF-B/c-sis mRNAs (3.5 kb and 2.6 kb) expressed in normal developing rat brain. In contrast to the constitutive expression of 3.5 kb mRNA, the expression of 2.6 kb mRNA increased markedly in accordance with those stages of brain development at which we had previously demonstrated an increased immunoreactivity for PDGF-B/c-SIS in neurons (Sasahara ef al., 1992). By PCR cloning and the RNase protection assay, we determined the complete sequence of rat PDGF-B/c-sis, and found that the 2.6 kb transcript was a form of the 3.5 kb message truncated at the 5' end, and that the predominant 2.6 kb mRNA commenced 15 nt upstream of the signal peptide, Accordingly, it is suggested that the truncation of 5' UTS contributes to the expression of PDGF-B/c-SIS protein in the CNS, Lack of translational inhibitory 5' UTS of PDGF-B/c-sis transcript and resultant efficient protein translation have been reported in only a few transformed cells and cultured umbilical vein endothelial cells, We have extended this knowledge to the developing rat brain, and suggest that a similar mechanism could operate widely in non-transformed tissue in vivo.