Conditional knockout of tumor overexpressed gene in mouse neurons affects RNA granule assembly, granule translation, LTP and short term habituation.
Conditional knockout of tumor overexpressed gene in mouse neurons affects RNA granule assembly, granule translation, LTP and short term habituation.
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DOI：
10.1371/journal.pone.0069989
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Carson JH
中科院分区：
文献类型：
--
作者：
Barbarese E;Ifrim MF;Hsieh L;Guo C;Tatavarty V;Maggipinto MJ;Korza G;Tutolo JW;Giampetruzzi A;Le H;Ma XM;Levine E;Bishop B;Kim DO;Kuwada S;Carson JH
在神经元中，特定的RNA组装成颗粒，颗粒被翻译成树突，然而颗粒组装的功能后果尚不清楚。肿瘤过表达基因(TOG)是一种颗粒相关蛋白，含有异质性核糖核蛋白(HnRNP)A2的多个结合位点，是识别存在于几个颗粒RNA中的称为hnRNP A2反应元件(A2RE)的顺式作用序列的另一个颗粒成分。颗粒中的翻译是零星的，被认为反映了单体翻译，偶尔会爆发，被认为反映了多体翻译。在本研究中，利用cre/lox技术对小鼠海马神经元TOG表达进行条件性敲除。在TOG中，CKO培养的神经元颗粒组装和活性调节细胞骨架相关(ARC)mRNA的突发性翻译被破坏，A2RE RNA。在TOG中，CKO脑片突触敏感性和长时程增强(LTP)降低。TOG CKO小鼠表现出多动、持之以恒和短期习服受损。这些结果表明，在海马神经元中，TOG是颗粒组装、颗粒平移和突触可塑性所必需的，并影响行为。
In neurons, specific RNAs are assembled into granules, which are translated in dendrites, however the functional consequences of granule assembly are not known. Tumor overexpressed gene (TOG) is a granule-associated protein containing multiple binding sites for heterogeneous nuclear ribonucleoprotein (hnRNP) A2, another granule component that recognizes cis-acting sequences called hnRNP A2 response elements (A2REs) present in several granule RNAs. Translation in granules is sporadic, which is believed to reflect monosomal translation, with occasional bursts, which are believed to reflect polysomal translation. In this study, TOG expression was conditionally knocked out (TOG cKO) in mouse hippocampal neurons using cre/lox technology. In TOG cKO cultured neurons granule assembly and bursty translation of activity-regulated cytoskeletal associated (ARC) mRNA, an A2RE RNA, are disrupted. In TOG cKO brain slices synaptic sensitivity and long term potentiation (LTP) are reduced. TOG cKO mice exhibit hyperactivity, perseveration and impaired short term habituation. These results suggest that in hippocampal neurons TOG is required for granule assembly, granule translation and synaptic plasticity, and affects behavior.
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