A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations.
A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations.
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DOI：
10.1186/s12864-017-4409-8
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发表时间：
2018-01-08
期刊：
影响因子：
4.4
通讯作者：
Gaisler-Salomon I
中科院分区：
文献类型：
--
作者：
Zaidan H;Ramaswami G;Golumbic YN;Sher N;Malik A;Barak M;Galiani D;Dekel N;Li JB;Gaisler-Salomon I
腺苷转肌苷（A-to-I）RNA编辑是由作用于RNA的腺苷脱氨酶（ADAR）催化的表观遗传修饰，在大脑中尤其普遍。我们使用高度精确的基于微流体的多重PCR测序（mmPCR-seq）技术来评估发育和环境压力对大鼠前额叶皮层和杏仁核中146个预先选择的保守位点的A-to-I编辑的影响。此外，我们询问是否可以在压力暴露大鼠的后代中观察到编辑的变化。同时，我们评估了ADAR表达水平的变化。与以前的研究一致，我们发现与新生大鼠大脑相比，成年大鼠大脑中的编辑通常更高。在出生时，前额叶皮层的编辑通常低于杏仁核。压力影响5-羟色胺受体2c（Htr 2c）的编辑，在两代人中暴露于生殖前压力的大鼠的后代中，该位点的编辑发生了显着变化。用mmPCR-seq测量的Htr 2c编辑的应激诱导的变化与用桑格和Illumina测序测量的变化相当。发育和应激诱导的阿达尔和Adarb 1 mRNA表达的变化进行了观察，但没有相关的编辑变化。我们的研究结果表明，mmPCR-seq可以准确地检测大鼠大脑样本中的A-to-I RNA编辑，并证实了先前关于RNA编辑率发育增加的说法。我们的研究结果还指出，青春期的压力是一种环境因素，它会改变几代人之后的RNA编辑模式，这也加入了越来越多描述压力跨代影响的文献。本文的在线版本（10.1186/s12864-017-4409-8）包含补充材料，可供授权用户使用。
Adenosine-to-inosine (A-to-I) RNA editing is an epigenetic modification catalyzed by adenosine deaminases acting on RNA (ADARs), and is especially prevalent in the brain. We used the highly accurate microfluidics-based multiplex PCR sequencing (mmPCR-seq) technique to assess the effects of development and environmental stress on A-to-I editing at 146 pre-selected, conserved sites in the rat prefrontal cortex and amygdala. Furthermore, we asked whether changes in editing can be observed in offspring of stress-exposed rats. In parallel, we assessed changes in ADARs expression levels. In agreement with previous studies, we found editing to be generally higher in adult compared to neonatal rat brain. At birth, editing was generally lower in prefrontal cortex than in amygdala. Stress affected editing at the serotonin receptor 2c (Htr2c), and editing at this site was significantly altered in offspring of rats exposed to prereproductive stress across two generations. Stress-induced changes in Htr2c editing measured with mmPCR-seq were comparable to changes measured with Sanger and Illumina sequencing. Developmental and stress-induced changes in Adar and Adarb1 mRNA expression were observed but did not correlate with editing changes. Our findings indicate that mmPCR-seq can accurately detect A-to-I RNA editing in rat brain samples, and confirm previous accounts of a developmental increase in RNA editing rates. Our findings also point to stress in adolescence as an environmental factor that alters RNA editing patterns several generations forward, joining a growing body of literature describing the transgenerational effects of stress. The online version of this article (10.1186/s12864-017-4409-8) contains supplementary material, which is available to authorized users.
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DOI：
10.3109/10253890.2015.1073254
发表时间：
2015-01-01
影响因子：
2.3
作者：
Brande-Eilat, Noa;Golumbic, Yaela N.;Gaisler-Salomon, Inna
通讯作者：
Gaisler-Salomon, Inna
DOI：
10.1016/s0169-328x(03)00317-6
发表时间：
2003-10-07
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Barbon, A;Vallini, I;Barlati, S
通讯作者：
Barlati, S
影响因子：
6.6
作者：
Beveridge, Natalie J.;Santarelli, Danielle M.;Cairns, Murray J.
通讯作者：
Cairns, Murray J.
影响因子：
64.8
作者：
Burns, CM;Chu, H;Emeson, RB
通讯作者：
Emeson, RB
影响因子：
3.1
作者：
Bock, Joerg;Poeschel, Julia;Poeggel, Gerd
通讯作者：
Poeggel, Gerd