Highlights • mRNA deadenylation is essential for female reproductive endocrine regulation • CNOT6/6L are specific molecular targets of FSH in granulosa cells • FSH-induced clearance of a subset of mRNAs in granulosa cells is CNOT6/6L dependent • The CCR4-NOTCNOT6/6L deadenylase are indispensable in female reproduction Summary CCR4-NOT deadenylase is a major regulator of mRNA turnover. It contains two heterogeneous catalytic subunits CNOT7/8 and CNOT6/6L in vertebrates.