Maternal factor PABPN1L is essential for maternal mRNA degradation during maternal-to-zygotic transition

Abstract

Infertilityaffects 10% -15% of familiesworldwide. However, the pathogenesis of female infertility caused by abnormal early embryonic development is not clear. We constructeda mouse model (Pabpn1l-/-) simulatingthe splicing abnormality of human PABPN1Landfound that the female was sterile and the male was fertile. The Pabpn1l-/-oocytes can be produced, ovulated and fertilized normally, but cannot develop beyond the 2-cell stage. UsingRNA-Seq, we found a large-scale upregulation of RNA in Pabpn1l-/-MII oocytes. Of the 2401 transcripts upregulatedin Pabpn1l-/-MII oocytes, 1523transcripts (63.4%) were also upregulatedin Btg4-/-MII oocytes, while only 53transcripts (2.2%) were upregulatedin Ythdf2-/-MII oocytes. We documentedthat transcripts in zygotes derived from Pabpn1l -/-oocytes have a longer poly(A) tail than the control group, aphenomenon similar to that in Btg4-/-mice. Surprisingly,the poly(A) tail of these mRNAswas significantly shorter in the Pabpn1l -/-MII oocytes than in the Pabpn1l +/+. Theseresults suggest that PABPN1L is involved in BTG4-mediated maternal mRNA degradation, and may antagonizepoly(A) tail shortening in oocytesindependentlyof its involvement in maternalmRNA degradation. Thus,PABPN1L variants could be a genetic marker offemale infertility.