TY - JOUR
T1 - Initiation of meiotic development is controlled by three post-transcriptional pathways in caenorhabditis elegans
AU - Mohammad, Ariz
AU - Vanden Broek, Kara
AU - Wang, Christopher
AU - Daryabeigi, Anahita
AU - Jantsch, Verena
AU - Hansen, Dave
AU - Schedl, Tim
N1 - Funding Information:
We thank our colleagues in the germline and meiosis fields for antibodies, helpful discussions, and software: Swathi Arur, Rafal Ciosk, Arshad Desai, Abby Dernburg, Yumi Kim, Judith Kimble, Edward Kipreos, Josef Loidl, Barbara Meyer, Hannah Seidel, Aaron Severson, Anne Villeneuve, and Monique Zetka. We thank Carrie Shemanko for use of tissue culture facilities. We thank WormBase, funded by the National Human Genome Research Institute; the Caenorhabditis Genetics Center, funded by National Institutes of Health Office of Research Infrastructure Programs (P40 OD-010440); and Shohei Mitani and the Japanese National Bioresource Project for strains. This work is supported by National Institutes of Health R01 GM-100756 to T.S., from the Natural Sciences and Engineering Research Council of Canada (NSERC) to D.H., and the Austrian Science Fund (SFB F3415-B19) to V.J.
Publisher Copyright:
© 2018 by the Genetics Society of America.
PY - 2018/8
Y1 - 2018/8
N2 - 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.
AB - 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.
KW - GLD-1
KW - GLD-2
KW - Germline
KW - Meiotic development
KW - Meiotic entry
KW - PROM-1
KW - SCF
UR - http://www.scopus.com/inward/record.url?scp=85050744321&partnerID=8YFLogxK
U2 - 10.1534/genetics.118.300985
DO - 10.1534/genetics.118.300985
M3 - Article
C2 - 29941619
AN - SCOPUS:85050744321
SN - 0016-6731
VL - 209
SP - 1197
EP - 1224
JO - Genetics
JF - Genetics
IS - 4
ER -