Specific processing of meiosis related transcript is linked to final maturation in human oocytes

Human meiosis in oocytes entails a fine regulation of the transcriptome to support late oocyte growth and early embryo development, both key to reproductive success. Currently, little is known about the co- and post-transcriptional mRNA processing mechanisms regulating the last meiotic passages, which contribute to transcriptome complexity and influence translation rates. We analyzed gene expression changes, splicing and pre-mRNA processing in an RNA sequencing set of 40 oocytes at different meiotic maturation stages, both in vivo ovulated and matured in vitro. We found abundant UTR processing, mostly at the 3’-, of meiosis-related genes between the stages of GV and MII, supported by the differential expression of spliceosome and pre-mRNA processing related genes. Importantly, we found very little differences among GV oocytes across several lengths of in vitro maturation, as long as they did not reach MII, suggesting a specific association of RNA processing and successful meiosis transit. Changes in protein isoforms are minor, though specific and consistent for genes involved in chromosome organization and spindle assembly. In conclusion, we reveal a dynamic transcript remodeling during human female meiosis, and show how pre-mRNA processing, specifically 3’-UTR shortening, drives a selective translational regulation of transcripts necessary to reach the final meiotic maturation. For single-cell RNA sequencing analysis, 40 oocytes at different maturation stages were collected: 10 oocytes were included in the study as GV immediately after ovum pick-up, 10 as MII after in vitro maturation (IVM, IVM-MII), 10 as GV that failed to mature after IVM (FTM-GV) and 10 MII were collected in vivo (IVO-MII) and included in the study after vitrification/warming. **Raw data and processed data are not provided due to the EU's General Data Protection Regulation (GDPR)**