Single-cell full-length isoform sequencing reveals an abundance of 3’ prime partial transcripts in maternally inherited RNAs

Abstract Isoform expression in preimplantation embryos has been extensively investigated, and many novel isoforms have been identified. However, the regulation patterns of different types of transcripts along the developing stages remainsunexplored. We quantified the expression of full-length isoforms in over one hundred single blastomeres from the mouse oocyte to blastocyst stage and found that the 3’ prime partial transcripts that lack stop codonswere highly accumulated in oocytes and zygotes. A typical 3’ prime partial isoform,Ncl-S-350, was demonstratedto be not a transcription by-productbutto function in the ZGA process. SRSF4 was identified to be responsible for generating these 3’ prime partial transcripts in mouse embryonic stem cells (mESCs), and both Ncl-S-350 and Srsf4 overexpression could convert mESCs to a 2-cell (2C)-like state. Our work reveals the important role of isoform switch regulation in early embryonic development and lays the foundation for an alternative way of acquiring totipotent cells.