Quantitative analysis of focused a-to-I RNA editing sites by ultra-high-throughput sequencing in psychiatric disorders.
Quantitative analysis of focused a-to-I RNA editing sites by ultra-high-throughput sequencing in psychiatric disorders.
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通过超高通量测序对精神疾病中集中的 a-to-I RNA 编辑位点进行定量分析。
DOI：
10.1371/journal.pone.0043227
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Roth BL
中科院分区：
文献类型：
--
作者：
Zhu H;Urban DJ;Blashka J;McPheeters MT;Kroeze WK;Mieczkowski P;Overholser JC;Jurjus GJ;Dieter L;Mahajan GJ;Rajkowska G;Wang Z;Sullivan PF;Stockmeier CA;Roth BL
A-to-I RNA 编辑是通过腺苷脱氨基作用对 RNA 中的单核苷酸进行转录后修饰，从而使基因组中编码的基因产物多样化。最近的研究已经鉴定出数千个潜在的 RNA 编辑位点（例如参见 Li 等人，Science 2009）；然而，其中只有少数网站得到了独立证实。在这里，我们通过超高通量测序（uHTS）系统地、定量地检查了三组正常人脑样本中的 109 个假定编码区 A-to-I RNA 编辑位点。 109 个假定位点中的 40 个（包括 25 个先前确认的位点）被验证为在我们的大脑样本中进行了真正的编辑，这表明 Li 等人（2009）高估了这些假定位点中的 A-to-I RNA 编辑。为了评估人类疾病中的 RNA 编辑，我们使用 uHTS 分析了重度抑郁症和精神分裂症受试者中的 29 个已确认位点。与许多先前的研究形成鲜明对比的是，我们没有发现这些患者样本中任何编辑位点的 RNA 编辑频率发生显着变化，包括 5HT2C 血清素受体 (HTR2C)。我们的结果表明，uHTS 是一种快速、定量和高通量的方法，用于评估人类生理和疾病中的 RNA 编辑，并且许多先前的 RNA 编辑研究可能高估了我们在人脑中检查的位点的 RNA 编辑的程度和与疾病相关的变异性。
A-to-I RNA editing is a post-transcriptional modification of single nucleotides in RNA by adenosine deamination, which thereby diversifies the gene products encoded in the genome. Thousands of potential RNA editing sites have been identified by recent studies (e.g. see Li et al, Science 2009); however, only a handful of these sites have been independently confirmed. Here, we systematically and quantitatively examined 109 putative coding region A-to-I RNA editing sites in three sets of normal human brain samples by ultra-high-throughput sequencing (uHTS). Forty of 109 putative sites, including 25 previously confirmed sites, were validated as truly edited in our brain samples, suggesting an overestimation of A-to-I RNA editing in these putative sites by Li et al (2009). To evaluate RNA editing in human disease, we analyzed 29 of the confirmed sites in subjects with major depressive disorder and schizophrenia using uHTS. In striking contrast to many prior studies, we did not find significant alterations in the frequency of RNA editing at any of the editing sites in samples from these patients, including within the 5HT2C serotonin receptor (HTR2C). Our results indicate that uHTS is a fast, quantitative and high-throughput method to assess RNA editing in human physiology and disease and that many prior studies of RNA editing may overestimate both the extent and disease-related variability of RNA editing at the sites we examined in the human brain.
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DOI：
10.1523/jneurosci.3896-08.2008
发表时间：
2008-11-26
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kawahara Y;Grimberg A;Teegarden S;Mombereau C;Liu S;Bale TL;Blendy JA;Nishikura K
通讯作者：
Nishikura K
影响因子：
16.6
作者：
通讯作者：
--
影响因子：
16.8
作者：
Bhalla, T;Rosenthal, JJC;Reenan, R
通讯作者：
Reenan, R
影响因子：
64.8
作者：
Burns, CM;Chu, H;Emeson, RB
通讯作者：
Emeson, RB
影响因子：
1.7
作者：
Dracheva, Stella;Chin, Benjamin;Haroutunian, Vahram
通讯作者：
Haroutunian, Vahram