Biophysics Graduate Program, The Ohio State University, Columbus, Ohio, United States of America.
PLoS Comput Biol. 2012;8(2):e1002400. doi: 10.1371/journal.pcbi.1002400. Epub 2012 Feb 23.
RNA editing describes the process in which individual or short stretches of nucleotides in a messenger or structural RNA are inserted, deleted, or substituted. A high level of RNA editing has been observed in the mitochondrial genome of Physarum polycephalum. The most frequent editing type in Physarum is the insertion of individual Cs. RNA editing is extremely accurate in Physarum; however, little is known about its mechanism. Here, we demonstrate how analyzing two organisms from the Myxomycetes, namely Physarum polycephalum and Didymium iridis, allows us to test hypotheses about the editing mechanism that can not be tested from a single organism alone. First, we show that using the recently determined full transcriptome information of Physarum dramatically improves the accuracy of computational editing site prediction in Didymium. We use this approach to predict genes in the mitochondrial genome of Didymium and identify six new edited genes as well as one new gene that appears unedited. Next we investigate sequence conservation in the vicinity of editing sites between the two organisms in order to identify sites that harbor the information for the location of editing sites based on increased conservation. Our results imply that the information contained within only nine or ten nucleotides on either side of the editing site (a distance previously suggested through experiments) is not enough to locate the editing sites. Finally, we show that the codon position bias in C insertional RNA editing of these two organisms is correlated with the selection pressure on the respective genes thereby directly testing an evolutionary theory on the origin of this codon bias. Beyond revealing interesting properties of insertional RNA editing in Myxomycetes, our work suggests possible approaches to be used when finding sequence motifs for any biological process fails.
RNA 编辑是指在信使 RNA 或结构 RNA 中插入、删除或替换单个或短片段核苷酸的过程。在多头绒泡菌的线粒体基因组中观察到了高水平的 RNA 编辑。多头绒泡菌最常见的编辑类型是插入单个 C。多头绒泡菌的 RNA 编辑非常准确;然而,其机制知之甚少。在这里,我们展示了分析黏菌中的两个生物体,即多头绒泡菌和双滴虫,如何使我们能够测试关于编辑机制的假设,这些假设不能仅从单个生物体进行测试。首先,我们表明,使用最近确定的多头绒泡菌的完整转录组信息,可以极大地提高在双滴虫中计算编辑位点预测的准确性。我们使用这种方法来预测双滴虫线粒体基因组中的基因,并鉴定出六个新的编辑基因以及一个似乎未编辑的新基因。接下来,我们研究了两个生物体之间编辑位点附近的序列保守性,以根据增加的保守性识别包含编辑位点位置信息的位点。我们的结果表明,编辑位点两侧仅九个或十个核苷酸内包含的信息(以前通过实验提出的距离)不足以定位编辑位点。最后,我们表明,这两个生物体中 C 插入 RNA 编辑的密码子位置偏倚与各自基因上的选择压力相关,从而直接测试了关于这种密码子偏倚起源的进化理论。除了揭示黏菌中插入性 RNA 编辑的有趣特性外,我们的工作还提出了在寻找任何生物学过程的序列基序失败时可能使用的方法。