SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
Elife. 2021 Sep 20;10:e67991. doi: 10.7554/eLife.67991.
Circular RNAs (circRNAs) are found across eukaryotes and can function in post-transcriptional gene regulation. Their biogenesis through a circle-forming backsplicing reaction is facilitated by reverse-complementary repetitive sequences promoting pre-mRNA folding. Orthologous genes from which circRNAs arise, overall contain more strongly conserved splice sites and exons than other genes, yet it remains unclear to what extent this conservation reflects purifying selection acting on the circRNAs themselves. Our analyses of circRNA repertoires from five species representing three mammalian lineages (marsupials, eutherians: rodents, primates) reveal that surprisingly few circRNAs arise from orthologous exonic loci across all species. Even the circRNAs from orthologous loci are associated with young, recently active and species-specific transposable elements, rather than with common, ancient transposon integration events. These observations suggest that many circRNAs emerged convergently during evolution - as a byproduct of splicing in orthologs prone to transposon insertion. Overall, our findings argue against widespread functional circRNA conservation.
环状 RNA(circRNAs)存在于真核生物中,可在转录后基因调控中发挥作用。通过反向互补重复序列促进前体 mRNA 折叠的环化拼接反应来实现它们的生物发生。环状 RNA 起源的同源基因总体上比其他基因具有更强的保守剪接位点和外显子,但仍不清楚这种保守性在多大程度上反映了对环状 RNA 本身的净化选择。我们对来自五个代表三个哺乳动物谱系(有袋动物、真兽类:啮齿动物、灵长类)的物种的环状 RNA 库进行的分析表明,令人惊讶的是,在所有物种中,只有少数环状 RNA 是从同源外显子基因座产生的。即使是来自同源基因座的环状 RNA 也与年轻的、最近活跃的和物种特异性的转座元件相关,而不是与常见的、古老的转座子整合事件相关。这些观察结果表明,许多环状 RNA 是在进化过程中趋同出现的,作为易受转座子插入的同源物剪接的副产物。总的来说,我们的研究结果反对广泛的功能环状 RNA 保守性。