MAPK signaling couples SCF-mediated degradation of translational regulators to oocyte meiotic progression

RNA-binding proteins (RBPs) are important regulators of gene expression programs, especially during gametogenesis. How the abundance of particular RBPs is restricted to defined stages of meiosis remains largely elusive. Here, we report a molecular pathway that subjects two nonrelated but broadly evo...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2018-03, Vol.115 (12), p.E2772-E2781
Main Authors: Kisielnicka, Edyta, Minasaki, Ryuji, Eckmann, Christian R.
Format: Article
Language:English
Subjects:
Astrochemistry
Biodegradation
Biological Sciences
Cascades
Cdc4 protein
Cullin
Degradation
Destabilization
Differentiation
Gametogenesis
Gene expression
Germ cells
Kinases
MAP kinase
Meiosis
Molecular biology
Pachytene
Phosphorylation
PNAS Plus
Prophase
Proteins
Regulators
Ribonucleic acid
RNA
RNA-binding protein
RNA-protein interactions
Sex differentiation
Signaling
Substrates
Translation
Tumor suppressor genes
Ubiquitin
Ubiquitin-protein ligase
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Summary:RNA-binding proteins (RBPs) are important regulators of gene expression programs, especially during gametogenesis. How the abundance of particular RBPs is restricted to defined stages of meiosis remains largely elusive. Here, we report a molecular pathway that subjects two nonrelated but broadly evolutionarily conserved translational regulators (CPB-3/CPEB and GLD-1/STAR) to proteosomal degradation in Caenorhabditis elegans germ cells at the transition from pachytene to diplotene of meiotic prophase. Both RBPs are recognized by the same ubiquitin ligase complex, containing the molecular scaffold Cullin-1 and the tumor suppressor SEL-10/FBXW7 as its substrate recognition subunit. Destabilization of either RBP through this Skp, Cullin, F-box–containing complex (SCF) ubiquitin ligase appears to loosen its negative control over established target mRNAs, and presumably depends on a prior phosphorylation of CPB-3 and GLD-1 by MAPK (MPK-1), whose activity increases in mid- to late pachytene to promote meiotic progression and oocyte differentiation. Thus, we propose that the orchestrated degradation of RBPs via MAPK-signaling cascades during germ cell development may act to synchronize meiotic with sexual differentiation gene expression changes.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1715439115