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

Proceedings of the National Academy of Sciences of the United States of America
Edyta KisielnickaChristian R Eckmann

Abstract

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 expressio...Continue Reading

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Citations

Mar 7, 2020·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Yuxia WangWang Jidong
Jun 14, 2019·Development·Nadine L VastenhouwHoward D Lipshitz
Apr 13, 2021·Frontiers in Cell and Developmental Biology·Bing-Wang ZhaoZhen-Bo Wang

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