Abstract
Post-transcriptional regulatory mechanisms are widely used to influence cell fate decisions in germ cells, early embryos, and neurons. Many conserved cytoplasmic RNA regulatory proteins associate with each other and assemble on target mRNAs, forming ribonucleoprotein (RNP) complexes, to control the mRNAs translational output. How these RNA regulatory networks are orchestrated during development to regulate cell fate decisions remains elusive. We addressed this problem by focusing on Caenorhabditis elegans germline development, an exemplar of post-transcriptional control mechanisms. Here, we report the discovery of GLS-1, a new factor required for many aspects of germline development, including the oocyte cell fate in hermaphrodites and germline survival. We find that GLS-1 is a cytoplasmic protein that localizes in germ cells dynamically to germplasm (P) granules. Furthermore, its functions depend on its ability to form a protein complex with the RNA-binding Bicaudal-C ortholog GLD-3, a translational activator and P granule component important for similar germ cell fate decisions. Based on genetic epistasis experiments and in vitro competition experiments, we suggest that GLS-1 releases FBF/Pumilio from GLD-3 repression. This facilitates the sperm-to-oocyte switch, as liberated FBF represses the translation of mRNAs encoding spermatogenesis-promoting factors. Our proposed molecular mechanism is based on the GLS-1 protein acting as a molecular mimic of FBF/Pumilio. Furthermore, we suggest that a maternal GLS-1/GLD-3 complex in early embryos promotes the expression of mRNAs encoding germline survival factors. Our work identifies GLS-1 as a fundamental regulator of germline development. GLS-1 directs germ cell fate decisions by modulating the availability and activity of a single translational network component, GLD-3. Hence, the elucidation of the mechanisms underlying GLS-1 functions provides a new example of how conserved machinery can be developmentally manipulated to influence cell fate decisions and tissue development.
Highlights
Germ line and early embryonic gene expression rely largely on cytoplasmic mRNA control mechanisms, allowing for maximum flexibility of control [1]
The development of the C. elegans germ line is a paradigm in the study of translational regulatory networks, composed of conserved RNA-binding or modifying proteins that act as mRNA regulators
We report the discovery of GLS-1, a novel cytoplasmic protein, which we find to form a protein complex with the translational activator GLD-3/Bicaudal-C
Summary
Germ line and early embryonic gene expression rely largely on cytoplasmic mRNA control mechanisms, allowing for maximum flexibility of control [1]. Many conserved cytoplasmic RNA-binding and RNA-modifying proteins have been found to support germline development, by associating with mRNA molecules in RNP complexes In higher eukaryotes, these transacting factors can form larger RNP aggregates, termed germplasm granules [2,3,4]. These transacting factors can form larger RNP aggregates, termed germplasm granules [2,3,4] These RNPs are anticipated to confer germ cell identity and are important for germline development their developmental regulation is largely unknown. It remains to be determined how these RNP complexes are utilized in an organism-specific fashion to control protein synthesis, i.e. the mRNA’s translational output
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