Translation initiation of ornithine decarboxylase and nucleocytoplasmic transport of cyclin D1 mRNA are increased in cells overexpressing eukaryotic initiation factor 4E
Translation initiation of ornithine decarboxylase and nucleocytoplasmic transport of cyclin D1 mRNA are increased in cells overexpressing eukaryotic initiation factor 4E
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DOI：
10.1073/pnas.93.3.1065
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发表时间：
1996-02-06
影响因子：
11.1
通讯作者：
Sonenberg, N
中科院分区：
文献类型：
--
作者：
Rousseau, D;Kaspar, R;Sonenberg, N
结构m（7）GpppN（其中N是任何核苷酸），称为帽，存在于所有真核细胞mRNA的5'末端（除了细胞器）。真核生物起始因子4 E（eIF-4 E）与帽结合并促进翻译起始复合物的形成，eIF-4 E涉及细胞生长的控制，因为其过表达导致啮齿动物细胞的恶性转化并解除对HeLa细胞生长的调节。有人认为，eIF-4 E的过表达导致编码生长促进蛋白的翻译不良的mRNA的翻译增强。在eIF-4 E过表达的NIH 3 T3细胞中，几种蛋白质的表达增强，包括细胞周期蛋白D1和鸟氨酸脱羧酶（ODC），然而，这种增加的机制尚未阐明。在这里，我们研究了eIF-4 E增加细胞周期蛋白D1和ODC表达的模式，我们发现，细胞周期蛋白D1和ODC的增加与eIF-4 E过表达的程度成正比，两种不相互排斥的机制导致了这种增加，在eIF-4 E过表达的细胞中，ODC mRNA的翻译起始速率增加，因为mRNA与较重的多聚核糖体一起沉积。对于细胞周期蛋白D1 mRNA，翻译起始没有增加，但其在细胞质中的量增加，而总mRNA没有显著增加。在亲本NIH 3 T3细胞系中，cyclin D1 mRNA的大部分局限于细胞核，在eIF-4 E过表达细胞中，绝大多数mRNA存在于细胞质中。这些结果表明，eIF-4 E除了在翻译起始中起作用外，还直接或间接地影响mRNA的核质转运。
The structure m(7)GpppN (where N is any nucleotide), termed cap, is present at the 5' end of all eukaryotic cellular mRNAs (except organellar). The eukaryotic initiation factor 4E (eIF-4E) binds to the cap and facilitates the formation of translation initiation complexes, eIF-4E is implicated in control of cell growth, as its overexpression causes malignant transformation of rodent cells and deregulates HeLa cell growth, It was suggested that overexpression of eIF-4E results in the enhanced translation of poorly translated mRNAs that encode growth-promoting proteins, Indeed, enhanced expression of several proteins, including cyclin D1 and ornithine decarboxylase (ODC), was documented in elF-4E-overexpressing NIH 3T3 cells, However, the mechanism underlying this increase has not been elucidated, Here, we studied the mode by which eIF-4E increases the expression of cyclin D1 and ODC, We show that the increase in the amount of cyclin D1 and ODC is directly proportional to the degree of eIF-4E overexpression, Two mechanisms, which are not mutually exclusive, are responsible for the increase, In eIF-4E-overexpressing cells the rate of translation initiation of ODC mRNA was increased inasmuch as the mRNA sedimented with heavier polysomes, For cyclin D1 mRNA, translation initiation was not increased, but rather its amount in the cytoplasm increased, without a significant increase in total mRNA, Whereas, in the parental NIH 3T3 cell line, a large proportion of the cyclin D1 mRNA was confined to the nucleus, in eIF-4E-overexpressing cells the vast majority of the mRNA was present in the cytoplasm, These results indicate that eIF-4E affects directly or indirectly mRNA nucleocytoplasmic transport, in addition to its role in translation initiation.