以色列特拉维夫大学Oded Rechavi课题组近期的研究揭示了神经元小RNAs的跨代行为调控潜力。2019年6月，国际知名学术期刊《细胞》发表了这一成果。

神经系统的活动是否能够遗传给子代是未知的。之前的研究表明，在秀丽隐杆线虫中，亲代的反应能够通过可遗传的小RNA来跨代影响子代的基因表达。

在这项工作中，研究人员发现由神经元合成的RDE-4蛋白依赖的小RNA能够调控由生殖细胞扩增的内源性小干扰RNA（siRNA）并影响数代生殖细胞的基因表达。这些由神经元产生的小RNA进一步地通过与生殖细胞中的AGO蛋白质HRDE-1结合后来调控后代的驱化行为，并可影响至少三代。这些小RNA调控的靶基因中，研究人员鉴定到了一个保守的基因saeg-2，其能够在生殖细胞中跨代下调。因此，神经元生成的小RNA所参与的saeg-2基因沉默是线虫在压力条件下驱化行为所需的。这项研究揭示了神经元行为通过小RNA来实现跨代交流的机制。

附：英文原文

Title: Neuronal Small RNAs Control Behavior Transgenerationally

Author: Rachel Posner, Itai Antoine Toker, Olga Antonova, Ekaterina Star, Sarit Anava, Eran Azmon, Michael Hendricks, Shahar Bracha, Hila Gingold, Oded Rechavi

Issue&Volume: Jun 13, 2019 Volume 177Issue 7 

Abstract: It is unknown whether the activity of the nervous system can be inherited. In Caenorhabditis elegans nematodes, parental responses can transmit heritable small RNAs that regulate gene expression transgenerationally. In this study, we show that a neuronal process can impact the next generations. Neurons-specific synthesis of RDE-4-dependent small RNAs regulates germline amplified endogenous small interfering RNAs (siRNAs) and germline gene expression for multiple generations. Further, the production of small RNAs in neurons controls the chemotaxis behavior of the progeny for at least three generations via the germline Argonaute HRDE-1. Among the targets of these small RNAs, we identified the conserved gene saeg-2, which is transgenerationally downregulated in the germline. Silencing of saeg-2 following neuronal small RNA biogenesis is required for chemotaxis under stress. Thus, we propose a small-RNA-based mechanism for communication of neuronal processes transgenerationally.

DOI: https://doi.org/10.1016/j.cell.2019.04.029

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30448-9