High levels of RNA-editing site conservation amongst 15 laboratory mouse strains.
High levels of RNA-editing site conservation amongst 15 laboratory mouse strains.
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DOI：
10.1186/gb-2012-13-4-r26
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发表时间：
2012-04-23
期刊：
影响因子：
12.3
通讯作者：
Adams DJ
中科院分区：
文献类型：
--
作者：
Danecek P;Nellåker C;McIntyre RE;Buendia-Buendia JE;Bumpstead S;Ponting CP;Flint J;Durbin R;Keane TM;Adams DJ
腺苷到肌苷(A-to-I)编辑是ADAR脱氨酶对双链RNA进行的一种位置选择性转录后改变，对体内平衡和发育至关重要。最近，小鼠基因组计划产生了17个实验小鼠品系的基因组序列和丰富的变种目录。我们还从15个测序菌株的全脑RNA中生成了RNA-seq数据。在这里，我们提出了一种计算方法，该方法采用一组初始的转录组/基因组错配位点，并考虑到比对中的系统性偏差、单核苷酸变体调用和测序深度来过滤这些调用，以高精度地识别RNA编辑位点。我们将这种方法应用于我们的小鼠品系转录本小组，识别了7,389个编辑站点，估计错误发现率在2.9%到10.5%之间。这些编辑绝大多数是A-to-I类型的，不属于此类的不到2.4%，其中只有三个编辑不能被解释为对齐人工产物。我们在编码序列中验证了24个新的RNA编辑位点，其中包括Cacna1d基因上的两个非同义编辑，它们落入Cav1.2电压门控钙通道的IQ结构域部分，表明编辑在转录多样性的产生中具有潜在的作用。我们发现，尽管有两百多万年的进化差异，但在15个菌株中，编辑的站点和每个站点的编辑水平都非常一致。在CDS2基因中，我们发现了RNA编辑作用的证据，尽管基因组序列存在分歧，但RNA编辑仍能保留祖先的转录序列。
Adenosine-to-inosine (A-to-I) editing is a site-selective post-transcriptional alteration of double-stranded RNA by ADAR deaminases that is crucial for homeostasis and development. Recently the Mouse Genomes Project generated genome sequences for 17 laboratory mouse strains and rich catalogues of variants. We also generated RNA-seq data from whole brain RNA from 15 of the sequenced strains. Here we present a computational approach that takes an initial set of transcriptome/genome mismatch sites and filters these calls taking into account systematic biases in alignment, single nucleotide variant calling, and sequencing depth to identify RNA editing sites with high accuracy. We applied this approach to our panel of mouse strain transcriptomes identifying 7,389 editing sites with an estimated false-discovery rate of between 2.9 and 10.5%. The overwhelming majority of these edits were of the A-to-I type, with less than 2.4% not of this class, and only three of these edits could not be explained as alignment artifacts. We validated 24 novel RNA editing sites in coding sequence, including two non-synonymous edits in the Cacna1d gene that fell into the IQ domain portion of the Cav1.2 voltage-gated calcium channel, indicating a potential role for editing in the generation of transcript diversity. We show that despite over two million years of evolutionary divergence, the sites edited and the level of editing at each site is remarkably consistent across the 15 strains. In the Cds2 gene we find evidence for RNA editing acting to preserve the ancestral transcript sequence despite genomic sequence divergence.
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影响因子：
3
作者：
Slater GS;Birney E
通讯作者：
Birney E
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作者：
Li, Heng
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Li, Heng
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通讯作者：
Clamp, M
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通讯作者：
Emeson, RB
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作者：
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