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Genetics. 2018 Aug;209(4):1197-1224. doi: 10.1534/genetics.118.300985. Epub 2018 Jun 25.

Initiation of Meiotic Development Is Controlled by Three Post-transcriptional Pathways in Caenorhabditis elegans.

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Department of Genetics, School of Medicine, Washington University in St. Louis, Missouri 63110.
Department of Biological Sciences, University of Calgary, T2N 1N4, Canada.
Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, 1030, Austria.
Department of Genetics, School of Medicine, Washington University in St. Louis, Missouri 63110


A major event in germline development is the transition from stem/progenitor cells to entry into meiosis and gametogenesis. This transition requires downregulation of mitotic cell cycle activity and upregulation of processes associated with meiosis. We identify the Caenorhabditis elegans SCFPROM-1 E3 ubiquitin-ligase complex as functioning to downregulate mitotic cell cycle protein levels including cyclin E, WAPL-1, and KNL-2 at meiotic entry and, independently, promoting homologous chromosome pairing as a positive regulator of the CHK-2 kinase. SCFPROM-1 is thus a novel regulator of meiotic entry, coordinating downregulation of mitotic cell cycle proteins and promoting homolog pairing. We further show that SCFPROM-1 functions redundantly, in parallel to the previously described GLD-1 and GLD-2 meiotic entry pathways, downstream of and inhibited by GLP-1 Notch signaling, which specifies the stem cell fate. Accordingly, C. elegans employs three post-transcriptional pathways, SCFPROM-1-mediated protein degradation, GLD-1-mediated translational repression, and GLD-2-mediated translational activation, to control and coordinate the initiation of meiotic development.


GLD-1; GLD-2; PROM-1; SCF; germline; meiotic development; meiotic entry

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