CNOT6 regulates a novel pattern of mRNA deadenylation during oocyte meiotic maturation

Abstract

In many cell types, the length of the poly(A) tail of an mRNA is closely linked to its fate - a long tail is associated with active translation, a short tail with silencing and degradation. During mammalian oocyte development, two contrasting patterns of polyadenylation have been identified. Some mRNAs carry a long poly(A) tail during the growth stage and are actively translated, then become deadenylated and down-regulated during the subsequent stage, termed meiotic maturation. Other mRNAs carry a short tail poly(A) tail and are translationally repressed during growth, and their poly(A) tail lengthens and they become translationally activated during maturation. As well, a program of elimination of this ‘maternal’ mRNA is initiated during oocyte maturation. Here we describe a third pattern of polyadenylation: mRNAs are deadenylated in growing oocytes, become polyadenylated during early maturation and then deadenylated during late maturation. We show that the deadenylase, CNOT6, is present in cortical foci of oocytes and regulates deadenylation of these mRNAs, and that PUF-binding elements (PBEs) regulate deadenylation in mature oocytes. Unexpectedly, maintaining a long poly(A) tail neither enhances translation nor inhibits degradation of these mRNAs. Our findings implicate multiple machineries, more complex than previously thought, in regulating mRNA activity in oocytes.

Role of Cnot6l in maternal mRNA turnover

“…For further insight into the expression of the CCR4–NOT complex during OET, we analyzed transcript levels of individual components in RNA-sequencing (RNA-seq) data from OET in mouse ( 19 , 20 ), cow ( 21 ), and human ( 22 ) oocytes ( Fig 1D ). In mouse oocytes, Cnot6l mRNA level was approximately 10 times higher than Cnot6 , which is expressed during oocyte growth and is apparently not a dormant maternal mRNA ( 23 ). High Cnot6l and low Cnot6 expression during OET was also observed in cow but not in humans, where the level of Cnot6 transcript was higher in metaphase II (MII) eggs.…”

Connections between 3′ end processing and DNA damage response: Ten years later

“…However, deadenylation is not a DNA damage‐specific cellular response, as it is necessary to precisely regulate intracellular mRNA homeostasis in other physiological pathways (Y. B. Yan, ), such as removal of stem cell mRNAs in differentiating cells (Solana et al, ) and oocyte meiotic maturation (Vieux & Clarke, ).…”

“…B. Yan, 2014), such as removal of stem cell mRNAs in differentiating cells (Solana et al, 2013) and oocyte meiotic maturation (Vieux & Clarke, 2018).…”

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

“…How this maternal mRNA with shortened poly(A) escapes degradation in MII oocytes is be a question that can be explored in the future. In another study, Vieux and collaborators documented that lengthening the poly(A) tail could not inhibit mRNA degradation during oocyte maturation 33 . This finding supports the possibility that the poly(A) tail length of some mRNAs does not affect its degradation during oocyte maturation.…”