RNA Ligase RTCB-mediated mRNA Alternative Splicing is Required for Mouse Oocyte Development and Maintenance

Intron splicing of the pre-mRNA is usually coupled with the transcription elongation catalyzed by RNA polymerase. However, recent large-scale mRNA sequencing showed that introns are still retained in 5-10% of mRNA, these introns are named as exitrons. They are deleted in some special cells or conditions to deal with developmental transition or cellular stress response. The role of this mechanism in mammalian female reproduction is elusive so far. We found that RNA terminal phosphate cyclase B (RTCB) mainly regulated splicing of these transcripts related to p-CDK1, DNA methylation and DNA damage repair. On the one hand, it regulated the recovery of oocyte meiosis by affecting CDK1 activation. On the other hand, it also regulated the developmental potential of oocytes by influencing splicing of DNA methylation and DNA damage repair-related mRNA. In addition, it could also play a crucial role in follicular development. Rtcb deletion resulted in the accumulation of these maternal mRNAs containing unspliced introns, and the decline of the overall level of transcripts. As a result, Rtcb-/- female are sterile. Our study highlights the important role of RTCB-regulated non-canonical alternative splicing in female reproduction. A total of 6 samples were analyzed in this study, including WT and Rtcb knock-out oocytes from fully-grown GV stage. Each biological samples has three replicates.