Abstract:
Adar-mediated adenosine-to-inosine (A-to-I) RNA editing mainly occurs in nucleus and diversifies the transcriptome in a flexible manner. It has been a challenging task to identify beneficial editing sites from the sea of total editing events. The functional Ser>Gly auto-recoding site in insect Adar gene has uneditable Ser codons in ancestral nodes, indicating the selective advantage to having an editable status. Here, we extended this case study to more metazoan species, and also looked for all Drosophila recoding events with potential uneditable synonymous codons. Interestingly, in D. melanogaster, the abundant nonsynonymous editing is enriched in the codons that have uneditable counterparts, but the Adar Ser>Gly case suggests that the editable orthologous codons in other species are not necessarily edited. The use of editable versus ancestral uneditable codon is a smart way to infer the selective advantage of RNA editing, and priority might be given to these editing sites for functional studies due to the feasibility to construct an uneditable allele. Our study proposes an idea to narrow down the candidates of beneficial recoding sites. Meanwhile, we stress that the matched transcriptomes are needed to verify the conservation of editing events during evolution.
摘要:
Adar介导的腺苷到肌苷(A到I)RNA编辑主要发生在细胞核中,并以灵活的方式使转录组多样化。从整个编辑事件的海洋中识别有益的编辑站点一直是一项具有挑战性的任务。昆虫Adar基因中的功能Ser>Gly自动重新编码位点在祖先节点中具有不可编辑的Ser密码子,指示具有可编辑状态的选择性优势。这里,我们将这个案例研究扩展到更多的后生动物物种,并寻找所有具有潜在不可编辑同义密码子的果蝇重新编码事件。有趣的是,在黑腹D中,丰富的非同义词编辑丰富了具有不可编辑对应物的密码子,但AdarSer>Gly案例表明,其他物种中的可编辑直系同源密码子不一定被编辑。使用可编辑密码子与祖先不可编辑密码子是推断RNA编辑的选择性优势的明智方法,由于构建不可编辑等位基因的可行性,因此可能优先考虑这些编辑位点进行功能研究。我们的研究提出了一个想法,以缩小有利的重新编码站点的候选范围。同时,我们强调,需要匹配的转录组来验证进化过程中编辑事件的保守性。