The Drosophila fragile X mental retardation protein participates in the piRNA pathway
The Drosophila fragile X mental retardation protein participates in the piRNA pathway
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DOI：
10.1242/jcs.161810
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发表时间：
2015-06-01
影响因子：
4
通讯作者：
Giangrande, Angela
中科院分区：
文献类型：
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作者：
Bozzetti, Maria Pia;Specchia, Valeria;Giangrande, Angela
RNA 代谢控制多种生物过程，并且一类特定的小 RNA（称为 piRNA）通过沉默性腺中转座子和重复序列的表达来充当基因组守护者。 piRNA 通路的缺陷会影响基因组完整性和生育力。 piRNA 通路对人类疾病的病理生理机制可能产生的影响已成为深入研究的对象，最近的研究表明该通路在包括突触可塑性在内的体细胞过程中发挥着作用。 RNA 结合的脆性 X 智力低下蛋白（FMRP，也称为 FMR1）控制着翻译，其缺失会引发人类最常见的智力低下综合症以及性腺缺陷。在这里，我们首次证明果蝇 Fmr1（表示为 dFmr1）（FMRP 的果蝇直系同源物）的种系和体细胞表达在 piRNA 介导的途径中是必需的。此外，dFmr1 与茄子（一种 Argonaute 蛋白，也是该途径的关键参与者）在遗传和生化方面相互作用。我们的数据为理解脆性 X 细胞患者中观察到的表型提供了新的视角，并支持 piRNA 可能在神经系统中发挥作用的观点。
RNA metabolism controls multiple biological processes, and a specific class of small RNAs, called piRNAs, act as genome guardians by silencing the expression of transposons and repetitive sequences in the gonads. Defects in the piRNA pathway affect genome integrity and fertility. The possible implications in physiopathological mechanisms of human diseases have made the piRNA pathway the object of intense investigation, and recent work suggests that there is a role for this pathway in somatic processes including synaptic plasticity. The RNA-binding fragile X mental retardation protein (FMRP, also known as FMR1) controls translation and its loss triggers the most frequent syndromic form of mental retardation as well as gonadal defects in humans. Here, we demonstrate for the first time that germline, as well as somatic expression, of Drosophila Fmr1 (denoted dFmr1), the Drosophila ortholog of FMRP, are necessary in a pathway mediated by piRNAs. Moreover, dFmr1 interacts genetically and biochemically with Aubergine, an Argonaute protein and a key player in this pathway. Our data provide novel perspectives for understanding the phenotypes observed in Fragile X patients and support the view that piRNAs might be at work in the nervous system.