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Biology subjects

Fulka, H.

Publications and source records attributed to Fulka, H..

3 recordsLinked to original sources

Protamine sequence determines species-specific nuclear shape and histone retention

Nuclear shape observed after the forced expression of mouse or human Protamine 1 (PRM1) in fibroblasts led us to propose the hypothesis that PRM1 sequence plays an important role in imposing the overall shape of the protaminized nucleus. Comparison of mouse and human PRM1 sequence pointed to cysteines 15 and 29 as potential critical residues in the mouse PRM1 sequence inducing the characteristic mouse "hooked" nuclear sperm shape. To explore this idea, mice with mutations in PRM1 Cys15 and Cys29 were generated. These mice remained fertile with no significant changes in sperm count or protamine expression levels. However, modifications in sperm head shape were observed. Transmission electron microscopy revealed disrupted chromatin condensation in mutant sperm, with several morphological changes and a remarkable increase in histone retention. Overall, the findings suggest that species-specific PRM1 cysteine residue positions are crucial for nuclear shape determination and histone retention in spermatozoa.

developmental biology↗

Golden hamster piRNAs are necessary for early embryonic development and establishment of spermatogonia

PIWI-associated RNAs (piRNAs) support the germline by suppressing retrotransposons and genes. In mice, piRNAs are essential for spermatogenesis but not oogenesis. To test how this applies to other mammals, we deleted Mov10l1 helicase in golden hamster, whose piRNA pathway is configured more similarly to that of other mammals. Mov10l1-/- male hamsters showed impaired establishment of spermatogonia accompanied by transcriptome dysregulation and a surge in MYSERV retrotransposon expression. The rare viable spermatogenic cells showed a meiotic failure phenotype like Mov10l1-/- mice. Female Mov10l1-/- hamsters were sterile due to post-meiotic loss of developmental competence in zygotes. Unique phenotypes of Mov10l1-/- hamsters demonstrate the adaptive nature of piRNA-mediated control of genes and retrotransposons in order to confront emerging genomic threats or acquire new physiological roles.

molecular biology↗

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↗