Genetic Architectures of Quantitative Variation in RNA Editing Pathways
Genetic Architectures of Quantitative Variation in RNA Editing Pathways
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DOI：
10.1534/genetics.115.179481
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发表时间：
2016-02-01
期刊：
影响因子：
3.3
通讯作者：
Churchill, Gary A.
中科院分区：
文献类型：
--
作者：
Gu, Tongjun;Gatti, Daniel M.;Churchill, Gary A.
RNA编辑是指改变RNA碱基序列的转录后过程。最近，数百个新的RNA编辑靶点被报道出来。然而，决定特异性和编辑程度的机制尚不清楚。我们在遗传多样化的多亲本群体Diversity Outbred小鼠中检测了位点特异性编辑的定量变化，并绘制了改变C-to-U编辑的全局编辑比例和a -to- i编辑的特定位点的多态性位点。C-to-U编辑酶Apobec1的等位基因序列影响Apob和其他58个C-to-U编辑靶点的编辑效率。我们确定了49个A-to-I编辑位点，在编辑的转录本中存在多态性，从而改变编辑效率。与C-to-U编辑的共享遗传控制相比，大多数可变的A-to-I编辑位点是由RNA二级结构中编辑位点附近的局部核苷酸多态性决定的。我们的研究结果表明，RNA编辑是一种受遗传变异影响的数量性状，进化限制导致了两种典型RNA编辑类型中不同的遗传结构。
RNA editing refers to post-transcriptional processes that alter the base sequence of RNA. Recently, hundreds of new RNA editing targets have been reported. However, the mechanisms that determine the specificity and degree of editing are not well understood. We examined quantitative variation of site-specific editing in a genetically diverse multiparent population, Diversity Outbred mice, and mapped polymorphic loci that alter editing ratios globally for C-to-U editing and at specific sites for A-to-I editing. An allelic series in the C-to-U editing enzyme Apobec1 influences the editing efficiency of Apob and 58 additional C-to-U editing targets. We identified 49 A-to-I editing sites with polymorphisms in the edited transcript that alter editing efficiency. In contrast to the shared genetic control of C-to-U editing, most of the variable A-to-I editing sites were determined by local nucleotide polymorphisms in proximity to the editing site in the RNA secondary structure. Our results indicate that RNA editing is a quantitative trait subject to genetic variation and that evolutionary constraints have given rise to distinct genetic architectures in the two canonical types of RNA editing.