Gu Tongjun, Gatti Daniel M, Srivastava Anuj, Snyder Elizabeth M, Raghupathy Narayanan, Simecek Petr, Svenson Karen L, Dotu Ivan, Chuang Jeffrey H, Keller Mark P, Attie Alan D, Braun Robert E, Churchill Gary A
The Jackson Laboratory, Bar Harbor, Maine 04609.
Research Programme on Biomedical Informatics, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Hospital del Mar Medical Research Institute, Dr. Aiguader, 88 Barcelona, Spain The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06030.
Genetics. 2016 Feb;202(2):787-98. doi: 10.1534/genetics.115.179481. Epub 2015 Nov 27.
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.
RNA编辑是指改变RNA碱基序列的转录后过程。最近，已报道了数百个新的RNA编辑靶点。然而，决定编辑特异性和程度的机制尚未完全了解。我们在一个遗传多样的多亲群体——多样性远交小鼠中研究了位点特异性编辑的定量变异，并绘制了多态性位点图谱，这些位点可全局改变C到U编辑的编辑比率以及特定位点A到I编辑的编辑比率。C到U编辑酶Apobec1中的一个等位基因系列影响Apob和另外58个C到U编辑靶点的编辑效率。我们鉴定出49个A到I编辑位点，其编辑转录本中的多态性会改变编辑效率。与C到U编辑的共享遗传控制不同，大多数可变A到I编辑位点由RNA二级结构中靠近编辑位点的局部核苷酸多态性决定。我们的结果表明，RNA编辑是一种受遗传变异影响的数量性状，并且进化限制在两种典型的RNA编辑类型中产生了不同的遗传结构。
