Nucleotide levels regulate germline proliferation through modulating GLP-1/Notch signaling in C. elegans

Genes & Development
Congwu ChiMin Han

Abstract

Animals alter their reproductive programs to accommodate changes in nutrient availability, yet the connections between known nutrient-sensing systems and reproductive programs are underexplored, and whether there is a mechanism that senses nucleotide levels to coordinate germline proliferation is unknown. We established a model system in which nucleotide metabolism is perturbed in both the nematode Caenorhabditis elegans (cytidine deaminases) and its food (Escherichia coli); when fed food with a low uridine/thymidine (U/T) level, germline proliferation is arrested. We provide evidence that this impact of U/T level on the germline is critically mediated by GLP-1/Notch and MPK-1/MAPK, known to regulate germline mitotic proliferation. This germline defect is suppressed by hyperactivation of glp-1 or disruption of genes downstream from glp-1 to promote meiosis but not by activation of the IIS or TORC1 pathways. Moreover, GLP-1 expression is post-transcriptionally modulated by U/T levels. Our results reveal a previously unknown nucleotide-sensing mechanism for controlling reproductivity.

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Citations

Apr 26, 2016·Cell Cycle·Congwu Chi, Min Han
Oct 28, 2017·The Journal of Cell Biology·Nicole M Templeman, Coleen T Murphy
Jul 18, 2019·Proceedings of the National Academy of Sciences of the United States of America·Rahul SrivastavaHamsa Puthalakath
Aug 12, 2018·Nature Communications·Natsumi KanzakiTaisei Kikuchi
Jul 28, 2016·Current Opinion in Lipidology·Anaïs BriotM Luisa Iruela-Arispe
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Dec 5, 2019·Genetics·E Jane Albert Hubbard, Tim Schedl
Feb 8, 2021·Developmental Biology·Sabih RashidRichard Roy
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Oct 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Vinod K MonyEyleen J O'Rourke
Feb 3, 2016·Genes & Development·Cheng Shi, Coleen T Murphy

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