In maturing oocytes ZFP36L2 binds AU-rich elements in specific maternal mRNAs and also CNOT6L, a catalytic component of the CCR4-NOT RNA deadenylase complex (inferred from mouse homologs). Knockout of CNOT6L prevents degradation of maternal transcripts related to translation in maturing oocytes (inferred from mouse oocytes). Depletion or knockout of ZFP36L2 causes defects in oocyte maturation (inferred from mouse oocytes) and prevents degradation of maternal mRNAs related to histone demethylation and regulation of transcription (inferred from mouse homologs), therefore ZFP36L2 is believed to regulate degradation of specific mRNAs in oocytes.
ZFP36L2 bound to AU-rich elements of specific mRNAs recruits the CCR4-NOT complex via an interaction between ZFP36L2 and CNOT6L of the CCR4-NOT complex (inferred from mouse homologs). CNOT6L then deadenylates the mRNA, targeting the mRNA for degradation (inferred from mouse homologs).
Maternal transcripts are transcribed from the maternal genome and accumulate in the oocyte during oogenesis. A subset of these maternal transcripts is degraded during later development of the unfertilized oocyte and after fertilization of the oocyte. Maternal decay of maternal transcripts (M-decay, reviewed in Jian and Fan 2022) refers to the degradation of maternal transcripts by maternally provided factors such as ZFP36L2 (inferred from the mouse homolog in Chousal et al. 2018, Sha et al. 2018), BTG4 (inferred from the mouse homolog in Liu et al. 2016, Yu et al. 2016, Pasternak et al. 2016, Zhao et al. 2020), and AGO2 (inferred from the mouse homolog in Zhang et al. 2020). ZFP36L2 acting before fertilization and BTG4 acting after fertilization recruit the CCR4-NOT deadenylation complex to the mRNA to initiate degradation. AGO2 is primed with endogenous small interfering RNAs (endosiRNAs) produced from double-stranded RNAs that originate from specific loci. The resulting AGO2:endosiRNA complexes bind and hydrolyze complementary maternal mRNAs. Similar patterns of mRNA decay are observed in human and mouse zygotes (Sha et al. 2020).