Larcher Jean-Christophe, Gasmi Laila, Viranaïcken Wildriss, Eddé Bernard, Bernard Rozenn, Ginzburg Irith, Denoulet Philippe
Biochimie Cellulaire-CNRS UMR 7098, Université Paris-6, 9 quai Saint-Bernard, Bâtiment C-Case 265, Paris 75252, Cedex 05, France.
FASEB J. 2004 Nov;18(14):1761-3. doi: 10.1096/fj.04-1763fje. Epub 2004 Sep 13.
In neurons, the selective translocation of Tau mRNA toward axons is due to the presence of a nucleotide sequence located in its 3' untranslated region and serving as axonal targeting element. Using this RNA sequence as a probe by a Northwestern approach, we have detected several proteins that interact with the targeting RNA element and could potentially be involved in Tau mRNA translocation, translation halting, and/or stabilization. Among them, two proteins were identified as the interleukin enhancer binding factor 3 (Ilf3) and NF90, two isoforms derived from a single gene product through alternative splicing. Each protein comprises two double-stranded RNA binding motifs that can interact with the predicted stem-loop secondary structure of the axonal targeting element. Specific antibodies raised against common or specific peptide sequences showed that both Ilf3 and NF90 are polymorphic proteins that are detected in neuronal nuclei and cell bodies, as well as in the proximal neuritic segments. This observation favors the idea that Ilf3 and NF90 are part of a protein complex that escorts Tau mRNA toward the axon.
在神经元中，Tau mRNA向轴突的选择性转运是由于其3'非翻译区存在一个核苷酸序列，该序列作为轴突靶向元件。通过诺瑟杂交法使用该RNA序列作为探针，我们检测到了几种与靶向RNA元件相互作用的蛋白质，它们可能参与Tau mRNA的转运、翻译暂停和/或稳定。其中，两种蛋白质被鉴定为白细胞介素增强子结合因子3（Ilf3）和NF90，它们是通过可变剪接从单个基因产物衍生而来的两种异构体。每种蛋白质都包含两个双链RNA结合基序，可与轴突靶向元件的预测茎环二级结构相互作用。针对共同或特定肽序列产生的特异性抗体表明，Ilf3和NF90都是多态性蛋白质，在神经元细胞核、细胞体以及近端神经突节段中均可检测到。这一观察结果支持了Ilf3和NF90是护送Tau mRNA向轴突转运的蛋白质复合物一部分的观点。
