GSE208531
DIS3L2 clears terminal-uridylated RNA to ensure oocyte maturation and female fertility
During mammalian oocyte development, transcriptome undergoes accumulation in the oocyte growth phase and elimination in the oocyte maturation phase. At the transition point between growth and maturation, which is the germinal vesicle intact oocyte (GV), terminal uridylation labels RNA for degradation. In our study, we show that a small cohort of RNA are polyadenylated after tail uridylation (defined as uridylated-poly(A) RNA). Upon genetic depletion of DIS3L2 (Dis3l2cKO) in mouse oocytes, uridylated-poly(A) RNA is extensively stabilized and dominates the oocyte transcriptome, which results in increased transcriptome in Dis3l2cKO oocytes. Consequently, Dis3l2cKO female mice are infertile and almost all oocytes are arrested at the GV stage. Uridylated-poly(A) RNA generally has shorter poly(A) tails and lower translation activity. The uridylated-poly(A) RNA in Dis3l2cKO oocytes not only generates from the insufficient RNA degradation, but also comes from the tail dynamics of RNA. Our study demonstrates more possibilities of RNA fates after being terminally uridylated, and highlights the role of DIS3L2 in safeguarding the transcriptome by degrading uridylated-poly(A) RNA. Overall design: We performed transcriptome profiling using single oocyte RNA-seq (polyA RNA and total RNA) and single oocyte PAIso-seq. The single oocyte RNA-seq is done at GV and MII stages and the PAIso-seq is done at the GV stage.