Single-oocyte full-length isoform sequencing unveils the impact of transposable elements on RNA diversity and stability

Oocyte-specific isoforms play crucial roles in oocyte maturation, while current understanding of the oocyte transcriptome is mainly focused on gene level. Here, we utilize single-cell full-length isoform sequencing to detect entire transcripts in human and mouse oocytes. Isoform diversity during oocyte maturation is systematically profiled, including 7154 and 4875 putative novel human and mouse transcripts, respectively. More than half of novel isoforms are categorized as novel-not-in-catalog (NNC) and may serve specific functions in oocytes. For example, ARHGAP18 mainly encoded by novel isoforms colocalizes with microtubules, and targeted knockdown of novel isoforms disrupts oocyte maturation. Moreover, approximately 30% of NNC isoforms are derived from transposable elements, and their incorporation within transcripts could enhance isoform stability during oocyte maturation. Altogether, our findings represent a valuable resource showcasing the complexity and diversity of RNA isoforms in oocytes, as well as transposable element co-option for novel isoform generation and isoform stability enhancement.