Tracing the expression of circular RNAs in human pre-implantation embryos

Yujiao Dang, Liying Yan, Boqiang Hu, Xiaoying Fan, Yixin Ren, Rong Li, Ying Lian, Jie Yan, Qingqing Li, Yan Zhang, Min Li, Xiulian Ren, Jin Huang, Yuqi Wu, Ping Liu, Lu Wen, Chen Zhang, Yanyi Huang, Fuchou Tang, Jie Qiao

PolyA- RNAs have not been widely analyzed in human pre-implantation embryos due to the scarcity of materials. In particular, circular RNA (circRNA), a novel type of polyA- RNA, has not been characterized during human pre-implantation development. We systematically analyze polyA+ messenger RNAs (mRNAs) and polyA- RNAs in individual human oocytes and pre-implantation embryos using SUPeR-seq. We de novo identify 10,032 circRNAs from 2974 hosting genes. Most of these circRNAs are developmentally stage-specific and dynamically regulated. Many of them are maternally expressed, implying their potentially important regulatory functions in oogenesis and the formation of totipotent zygotes. Comparison between human and mouse embryos reveals both high conservation and clear distinction between these two species. Human pre-implantation embryos generate more types of circRNA compared with mouse embryos and this is associated with a striking increase of the length of the circRNA flanking introns in humans. We also perform RNA de novo assembly and identify novel transcript units, many of which are potentially novel long non-coding RNAs. This study reports the first analysis of the whole transcriptome comprising both polyA+ mRNAs and polyA- RNAs including circRNAs during human pre-implantation development. It provides an invaluable resource for analyzing the unique function and complex regulatory mechanisms of circRNAs during this process.