Yuen, W. S. | Search bioRxiv

bioRxiv2023

Fertility is compromised after oocyte-specific deletion of Katanin A-subunit, Katna1, but not Katnal1

Katanins are microtubule severing enzymes that play roles in shaping diverse microtubule-based structures during all cell cycle stages. To address the role of katanin A-subunits in mammalian oocytes, we have used the Zp3-CreLox approach to specifically delete katanin A1 (Katna1) and katanin A-like 1 (Katnal1) from the start of oocyte growth in mice. Here, we show that Katnal1 is not required for normal female fertility, but that deletion of Katna1 causes a 50% decrease in fertility. Further investigation in Katna1-/- oocytes revealed no effect on MI spindle morphology but a significant effect on the morphology of MII spindles. This was accompanied by a decreased rate of fertilisation. Resultant Katna1+/- heterozygous embryos that reached the 2-cell stage developed at normal rates to the blastocyst stage. Diploid homozygous parthenotes derived from Katna1-/- oocytes revealed a reduced rate of blastocyst formation, decreased cell number and increased nuclear size. The ability of the paternal allele to rescue preimplantation development suggests the origin of the decrease in the fertility of conditional Katna1-/- mice lies in abnormalities arising in the egg to embryo transition prior to embryonic genome activation.

developmental biology↗

bioRxiv2020

Changes in subcellular structures and states of Pumilio1 regulate the translation of target Mad2 and Cyclin B1 mRNAs

Temporal and spatial control of mRNA translation has emerged as a major mechanism for promoting diverse biological processes. However, the molecular nature of temporal control of translation remains unclear. In oocytes, many mRNAs are deposited as a translationally repressed form and are translated at appropriate timings to promote the progression of meiosis and development. Here, we show that changes in structures and states of the RNA-binding protein Pumilio1 regulate the translation of target mRNAs and progression of oocyte maturation. Pumilio1 was shown to bind to Mad2 and Cyclin B1 mRNAs, assemble highly clustered solid-like aggregates, and surround Mad2 and Cyclin B1 RNA granules in mouse oocytes. These Pumilio1 aggregates were dissolved by phosphorylation prior to the translational activation of target mRNAs. Stabilization of Pumilio1 aggregates prevented the translational activation of target mRNAs and oocyte maturation. Together, our results provide an aggregation-dissolution model for the temporal and spatial control of translation.

cell biology↗