An extended meiotic prophase is a hallmark of oogenesis in sexually reproducing animals. Arrest in meiotic prophase I coincides with the period of growth that presumably enables oocytes to acquire the cytoplasmic components needed to produce healthy progeny and to gain competence to complete meiosis. Meiotic resumption (also called meiotic maturation) involves the transition to metaphase I, and is triggered by maturation-promoting factor, which consists of the Cdk1 catalytic subunit and the cyclin B regulatory subunit. Because full-grown oocytes of most animals are transcriptionally quiescent, translational regulation is a major control point. Biochemical and genetic results suggest that LIN-41 controls mRNA translation to coordinate and control oocyte growth and meiotic maturation downstream of intercellular signaling. In the absence of LIN-41, pachytene-stage oocytes cellularize prematurely and fail to progress to diplotene. Instead, these cells activate CDK-1, enter M phase, and attempt to segregate chromosomes. Translational derepression of the CDK-1 activator CDC-25.3 contributes to premature M-phase entry in lin-41 mutant oocytes. LIN-41 copurifies with regulators of cytoplasmic polyadenylation, including the GLD-2 poly(A) polymerase and its cofactor GLD-3, which are thought to function as translational activators, suggesting that LIN-41 might regulate translational activation and repression. Consistent with this idea, the premature M-phase entry defect in lin-41 mutants requires gld-2 function–lin-41 gld-2 double mutant oocytes arrest in pachytene. Genetic analysis using classical and CRISPR-Cas9-induced alleles suggests the NHL domain, which constitutes a novel RNA-binding domain, is a chief determinant of LIN-41 function. Our results suggest that LIN-41 functions as a molecular “stop sign” that imposes prophase arrest. Further, genetic analysis also reveals that LIN-41 is not simply an arbiter of the meiotic maturation decision; its proper function is also required to form high-quality oocytes and to prevent aneuploidy. Upon the onset of meiotic maturation, LIN-41 is degraded in a CDK-1-dependent manner. Thus LIN-41 controls and coordinates oocyte growth and meiotic maturation to enable successful fertilization.
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