Abstract
Germ granules are protein-RNA condensates that segregate with the embryonic germline. In Caenorhabditis elegans embryos, germ (P) granule assembly requires MEG-3, an intrinsically disordered protein that forms RNA-rich condensates on the surface of PGL condensates at the core of P granules. MEG-3 is related to the GCNA family and contains an N-terminal disordered region (IDR) and a predicted ordered C-terminus featuring an HMG-like motif (HMGL). We find that MEG-3 is a modular protein that uses its IDR to bind RNA and its C-terminus to drive condensation. The HMGL motif mediates binding to PGL-3 and is required for co-assembly of MEG-3 and PGL-3 condensates in vivo. Mutations in HMGL cause MEG-3 and PGL-3 to form separate condensates that no longer co-segregate to the germline or recruit RNA. Our findings highlight the importance of protein-based condensation mechanisms and condensate-condensate interactions in the assembly of RNA-rich germ granules.
Highlights
In animals with germ plasm, specification of the germline depends on the segregation of maternal RNAs and proteins to the primordial germ cells
Much progress has been made in our understanding of stress granule assembly with the realization that stress granules resemble liquid condensates that assemble by liquid-liquid phase separation (LLPS)
We found that PGL-3 condensates co-localized with MEG-3Cterm condensates (37/37 PGL-3 condensates scored in P1; Figure 3B) as in wild-type
Summary
In animals with germ plasm, specification of the germline depends on the segregation of maternal RNAs and proteins (germline determinants) to the primordial germ cells. Germline determinants assemble in germ granules, micronsized dense assemblies that concentrate RNA and RNA-binding proteins Unlike the dynamic condensates assembled by LLPS in vitro, germ granules are not well-mixed, single-phase liquid droplets. In addition to PGL and MEG co-assemblies, P granules concentrate specific maternal transcripts (Parker et al, 2020; Seydoux and Fire, 1994). We identify a predicted ordered motif (HMGL) required for binding to PGL-3 in vitro that is essential to build MEG-3/PGL-3 co-assemblies that recruit RNA in vivo. IDR binds RNA and enriches MEG-3 in germ plasm but is not sufficient on its own to assemble RNA-rich condensates. Our observations highlight the importance of condensation driven by protein-protein interactions in the assembly of germ granules
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