ELAV tumor antigen, Hel-N1, increases translation of neurofilament M mRNA and induces formation of neurites in human teratocarcinoma cells
ELAV tumor antigen, Hel-N1, increases translation of neurofilament M mRNA and induces formation of neurites in human teratocarcinoma cells
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DOI：
10.1101/gad.13.4.449
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发表时间：
1999-02-15
影响因子：
10.5
通讯作者：
Keene, JD
中科院分区：
文献类型：
--
作者：
Antic, D;Lu, N;Keene, JD
人类 ELAV 蛋白通过调节细胞质中 mRNA 的表达参与细胞生长和分化。在用人神经元 ELAV 样蛋白 Hel-N1 转染的人胚胎畸胎癌 (hNT2) 细胞中，形成了神经突，但细胞并未终末分化。神经突形成与 Hel-N1 过表达相关的细胞也表达了沿神经突分布的内源性神经丝 M (NF-M) 蛋白水平升高。然而，无论 hNT2 细胞是否转染 Hel-N1，NP-M mRNA 的稳态水平仍然相似。这些发现表明 NF-M mRNA 的周转不受 Hel-N1 表达的影响，尽管事实上 Hel-N1 可以结合 NF-M mRNA 的 3' UTR，并且发现与转染细胞中的 NF-M mRNA 直接相关。对 Hel-N1 转染子中 NF-M mRNA 与翻译装置关联的分析显示，NF-M mRNA 几乎完全募集到重多核糖体中，表明 Hel-N1 导致翻译起始的增加。我们的结果表明，含有 ARE 的 mRNA 的稳定性和/或翻译可以由 ELAV 蛋白 Hel-N1 独立调节，具体取决于 3' UTR 中的序列元件以及体内与 Hel-N1 结合的 mRNA 的固有周转率。
Human ELAV proteins are implicated in cell growth and differentiation via regulation of mRNA expression in the cytoplasm. In human embryonic teratocarcinoma (hNT2) cells transfected with the human neuronal ELAV-Iike protein, Hel-N1, neurites formed, yet cells were not terminally differentiated. Cells in which neurite formation was associated with Hel-N1 overexpression, also expressed increased levels of endogenous neurofilament M (NF-M) protein, which distributed along the neurites. However, steady-state levels of NP-M mRNA remained similar whether or not hNT2 cells were transfected with Hel-N1. These findings suggest that turnover of NF-M mRNA was not affected by Hel-N1 expression, despite the fact that Hel-N1 can bind to the 3' UTR of NF-M mRNA and was found directly associated with NF-M mRNA in transfected cells. Analysis of the association of NF-M mRNA with the translational apparatus in Hel-N1 transfectants showed nearly complete recruitment to heavy polysomes, indicating that Hel-N1 caused an increase in translational initiation. Our results suggest that the stability and/or translation of ARE-containing mRNAs can be regulated independently by the ELAV protein, Hel-N1, depending upon sequence elements in the 3' UTRs and upon the inherent turnover rates of the mRNAs that are bound to Hel-N1 in vivo.