ELAV/Hu 蛋白对神经元 RNA 特征的调节,WIREs RNA

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ELAV/Hu 蛋白对神经元 RNA 特征的调节
WIREs RNA ( IF 6.4 ) Pub Date : 2022-04-15 , DOI: 10.1002/wrna.1733
Valérie Hilgers ₁

Affiliation

由高度保守的elav/Hu编码的 RNA 结合蛋白基因家族存在于所有后生动物中，在共转录和转录后水平调节多种基因的表达。神经系统特异性 ELAV/Hu 蛋白因其在神经元分化中的重要作用而突出，并且突变与人类神经发育和神经退行性疾病有关。果蝇 ELAV 是蛋白质家族的创始成员，它通过促进数百个基因的选择性剪接和选择性聚腺苷酸化来介导神经元 RNA 特征的合成。最近对 ELAV 直接 RNA 靶标的鉴定揭示了该蛋白质在塑造神经元转录组中的核心作用，并强调了神经元转录本特征对于神经元维持和生物体存活的重要性。动物已经进化出多种细胞机制来确保 ELAV/Hu 功能的稳健性。在果蝇中，elav以 3'UTR 依赖性方式自动调节以维持最佳蛋白质水平。ELAV 的完全缺失会导致正常细胞质旁系同源物 FNE 的激活和核定位，该过程称为 EXon 激活功能救援 (EXAR)。其他物种，包括哺乳动物，似乎利用不同的策略（例如蛋白质冗余）来维持 ELAV 蛋白质功能并有效保护神经元转录组的身份。

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Regulation of neuronal RNA signatures by ELAV/Hu proteins

The RNA-binding proteins encoded by the highly conserved elav/Hu gene family, found in all metazoans, regulate the expression of a wide range of genes, at both the co-transcriptional and posttranscriptional level. Nervous-system-specific ELAV/Hu proteins are prominent for their essential role in neuron differentiation, and mutations have been associated with human neurodevelopmental and neurodegenerative diseases. Drosophila ELAV, the founding member of the protein family, mediates the synthesis of neuronal RNA signatures by promoting alternative splicing and alternative polyadenylation of hundreds of genes. The recent identification of ELAV's direct RNA targets revealed the protein's central role in shaping the neuronal transcriptome, and highlighted the importance of neuronal transcript signatures for neuron maintenance and organism survival. Animals have evolved multiple cellular mechanisms to ensure robustness of ELAV/Hu function. In Drosophila, elav autoregulates in a 3′UTR-dependent manner to maintain optimal protein levels. A complete absence of ELAV causes the activation and nuclear localization of the normally cytoplasmic paralogue FNE, in a process termed EXon-Activated functional Rescue (EXAR). Other species, including mammals, seem to utilize different strategies, such as protein redundancy, to maintain ELAV protein function and effectively safeguard the identity of the neuronal transcriptome.

更新日期：2022-04-15

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