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

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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Chi C,Ronai D,Than MT,Walker CJ,Sewell AK,Han M

doi

10.1101/gad.275107.115

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

307-20

issue

3

eissn

0890-9369

issn

1549-5477

pii

30/3/307

journal_volume

30

pub_type

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