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Biology subjects

Schultz, R. M.

Publications and source records attributed to Schultz, R. M..

2 recordsLinked to original sources

Role of Cnot6l in maternal mRNA turnover

Removal of poly(A) tail is an important mechanism controlling eukaryotic mRNA turnover. The major eukaryotic deadenylase complex CCR4-NOT contains two deadenylase components, CCR4 and CAF1 for which mammalian CCR4 is encoded by Cnot6 or Cnot6l paralogs. We show that Cnot6l apparently supplies the majority of CCR4 in the maternal CCR4-NOT complex in mouse, hamster, and bovine oocytes. Deletion of Cnot6l yielded viable mice but Cnot6l-/- females exhibited ~40% smaller litter size. The main onset of the phenotype was post-zygotic: fertilized Cnot6l-/- eggs developed slower and arrested more frequently than Cnot6l+/- eggs suggesting that maternal CNOT6L is necessary for accurate oocyte-to-embryo transition (OET). Transcriptome analysis revealed major transcriptome changes in Cnot6l-/- ovulated eggs and 1-cell zygotes. In contrast, minimal transcriptome changes in preovulatory Cnot6l-/- oocytes were consistent with reported Cnot6l mRNA dormancy. A minimal overlap between transcripts sensitive to decapping inhibition and Cnot6l loss suggests that decapping and CNOT6L-mediated deadenylation selectively target distinct subsets of mRNAs during OET in mouse.

molecular biology

Spindle asymmetry drives non-Mendelian chromosome segregation

Genetic elements compete for transmission through meiosis, when haploid gametes are created from a diploid parent. Selfish elements can enhance their transmission through meiotic drive, in violation of Mendels Law of Segregation. In female meiosis, selfish elements drive by preferentially attaching to the egg side of the spindle, which implies some asymmetry between the two sides of the spindle, but molecular mechanisms underlying spindle asymmetry are unknown. Here we show that CDC42 signaling from the cell cortex regulates microtubule tyrosination to induce spindle asymmetry, and non-Mendelian segregation depends on this asymmetry. These signals depend on cortical polarization directed by chromosomes, which are positioned near the cortex to allow the asymmetric cell division. Thus, selfish meiotic drivers exploit the asymmetry inherent in female meiosis to bias their transmission.

cell biology