Abstract
We describe MIP-1 and MIP-2, novel paralogous C. elegans germ granule components that interact with the intrinsically disordered MEG-3 protein. These proteins promote P granule condensation, form granules independently of MEG-3 in the postembryonic germ line, and balance each other in regulating P granule growth and localization. MIP-1 and MIP-2 each contain two LOTUS domains and intrinsically disordered regions and form homo- and heterodimers. They bind and anchor the Vasa homolog GLH-1 within P granules and are jointly required for coalescence of MEG-3, GLH-1, and PGL proteins. Animals lacking MIP-1 and MIP-2 show temperature-sensitive embryonic lethality, sterility, and mortal germ lines. Germline phenotypes include defects in stem cell self-renewal, meiotic progression, and gamete differentiation. We propose that these proteins serve as scaffolds and organizing centers for ribonucleoprotein networks within P granules that help recruit and balance essential RNA processing machinery to regulate key developmental transitions in the germ line.
Highlights
The germ line is essential to the propagation of sexually reproducing multicellular organisms
In C. elegans adults, germ cells develop along an assembly line within a syncytium, migrating away from the stem cell niche as they proliferate through several rounds of mitosis, enter meiosis, and differentiate into gametes; mature oocytes are fertilized as they pass through a sperm storage organ called the spermatheca
We describe the first phenotypic and molecular characterization of C. elegans LOTUS domain proteins
Summary
The germ line is essential to the propagation of sexually reproducing multicellular organisms. A common feature of germ cells is the presence of germ granules, membraneless cytoplasmic compartments with liquid-like properties that form by liquid-liquid phase separation (LLPS) from the bulk cytoplasm (Brangwynne et al, 2009) Rich in both RNA and RNA-binding proteins (RBPs), germ granules contain a large number of molecules with roles in post-transcriptional RNA regulation and the preservation of genome integrity (Mayya and Duchaine, 2019). These complex ribonucleoprotein (RNP) assemblies are important for the specification, maintenance, and normal development of the germ line (Knutson et al, 2017).
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