Recently, Dr. Heng-Yu Fan’s lab at the Life Sciences Institute, Zhejiang University published their new findings at Nature Structural and Molecular Biology. The paper is entitled “BTG4 is a Meiotic Cell Cycle-Coupled Maternal-Zygotic Transition Licensing Factor in Oocytes”.

Remodeling a fertilized egg into a totipotent zygote is an important and complex cell transformation event in biology.  Maternal mRNAs, which are synthesized and stored during oocyte growth, serve as the maternal contribution that supports early embryo development but undergo general decay after meiotic resumption, while the zygotic genome is transcriptionally activated only at later cell cycles. This transition from a maternal to a zygotic mode of development is called the maternal-zygotic transition (MZT). Understanding of MZT in mammals is a cornerstone of assisted reproduction technology, because a large proportion of in vitro matured human oocytes are morphologically normal but demonstrate MZT defects after fertilization. However, only a limited number of maternal-effect genes that regulate MZT have been identified in mice.

Particularly, the mRNAs stored in oocytes undergo general decay during maternal-zygotic transition (MZT), and their stability is tightly interconnected with meiotic cell cycle progression. However, the factors that trigger maternal mRNA decay and couple this event to oocyte meiotic maturation remain elusive. In this paper, Dr. Fan’s group identified B-cell translocation gene-4 (BTG4) as an MZT licensing factor in mouse. BTG4 bridged CNOT7, a catalytic subunit of CCR4–NOT deadenylase, to eIF4E, a key translation initiation factor, and played a permissive role in maternal mRNA decay. Btg4 null females produce morphologically normal oocytes but are infertile due to early developmental arrest. Oocyte intrinsic MAPK cascade triggers translation of Btg4 mRNA stored in fully-grown oocytes by targeting its 3’-untranslated region, thereby couples CCR4–NOT deadenylase-mediated maternal mRNA decay with oocyte maturation and fertilization. This is a key step in oocyte cytoplasmic maturation that determines the developmental potential of mammalian embryos.

Text link: http://www.nature.com/nsmb/journal/vaop/ncurrent/full/nsmb.3204.html