Institute for Systems Biology, Jianghan University, Wuhan, Hubei, China.
Department of Computer Science and Engineering, Washington University, Saint Louis, MO, USA.
RNA Biol. 2020 Jan;17(1):87-97. doi: 10.1080/15476286.2019.1669391. Epub 2019 Sep 27.
Formed by back splicing or back fusion of linear RNAs, circular RNAs (circRNAs) constitute a new class of non-coding RNAs of eukaryotes. Recent studies reveal a spliceosome-dependent biogenesis of circRNAs where circRNAs arise at the intron-exon junctions of mRNAs. In this study, using a novel identification method, we show that circRNAs can originate from the interior regions of exons, introns, and intergenic transcripts in human, mouse and rice, which were referred to as (). Many i-circRNAs have some remarkable characteristics: multiple i-circRNAs may arise from the same genomic locus; their back fusion points may not be associated with the AG/GT splicing sites, but rather a new pair of motif AC/CT, their back fusion points are adjacent to complementary sequences; and they may circulate on short homologous sequences. We validated several i-circRNAs in HeLa cells by Polymerase Chain Reaction followed by Sanger sequencing. Our results combined showed that i-circRNAs are circRNAs, indicated novel biogenesis pathways independent of the splicing apparatus, and expanded our understanding of the origin, diversity, and complexity of circRNAs.
由线性 RNA 的反向剪接或融合形成，环状 RNA（circRNA）构成了真核生物中一类新的非编码 RNA。最近的研究揭示了 circRNA 的剪接体依赖性生物发生，其中 circRNA 出现在 mRNA 的内含子-外显子交界处。在这项研究中，我们使用一种新的鉴定方法表明，circRNA 可以起源于人类、小鼠和水稻的外显子、内含子和基因间转录本的内部区域，这些被称为（）。许多 i-circRNA 具有一些显著的特征：多个 i-circRNA 可能来自同一个基因组位点；它们的反向融合点可能与 AG/GT 剪接位点无关，而是与新的一对 motif AC/CT 相关，它们的反向融合点与互补序列相邻；并且它们可能在短的同源序列上循环。我们通过聚合酶链反应（PCR）和 Sanger 测序在 HeLa 细胞中验证了几个 i-circRNA。我们的结果表明，i-circRNA 是一类 circRNA，表明存在独立于剪接装置的新型生物发生途径，并扩展了我们对 circRNA 的起源、多样性和复杂性的理解。
