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Membraneless organelles are RNA–protein assemblies which have been implicated in post‐transcriptional control. Germ cells form membraneless organelles referred to as germ granules, which contain conserved proteins including Tudor domain‐containing scaffold polypeptides and their partner proteins that interact with Tudor domains. Here, we show that inDrosophila, different germ granule proteins associate with the multi‐domain Tudor protein using different numbers of Tudor domains. Furthermore, these proteins compete for interaction with Tudorin vitroand, surprisingly, partition to distinct and poorly overlapping clusters in germ granulesin vivo. This partition results in minimization of the competition. Our data suggest that Tudor forms structurally different configurations with different partner proteins which dictate different biophysical properties and phase separation parameters within the same granule.
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Germ Granule Evolution Provides Mechanistic Insight into Drosophila Germline Development
Abstract The copackaging of mRNAs into biomolecular condensates called germ granules is a conserved strategy to posttranscriptionally regulate germline mRNAs. In Drosophila melanogaster, mRNAs accumulate in germ granules by forming homotypic clusters, aggregates containing multiple transcripts from the same gene. Nucleated by Oskar (Osk), homotypic clusters are generated through a stochastic seeding and self-recruitment process that requires the 3′ untranslated region (UTR) of germ granule mRNAs. Interestingly, the 3′ UTR belonging to germ granule mRNAs, such as nanos (nos), have considerable sequence variations among Drosophila species and we hypothesized that this diversity influences homotypic clustering. To test our hypothesis, we investigated the homotypic clustering of nos and polar granule component (pgc) in four Drosophila species and concluded that clustering is a conserved process used to enrich germ granule mRNAs. However, we discovered germ granule phenotypes that included significant changes in the abundance of transcripts present in species’ homotypic clusters, which also reflected diversity in the number of coalesced primordial germ cells within their embryonic gonads. By integrating biological data with computational modeling, we found that multiple mechanisms underlie naturally occurring germ granule diversity, including changes in nos, pgc, osk levels and/or homotypic clustering efficacy. Furthermore, we demonstrated how the nos 3′ UTR from different species influences nos clustering, causing granules to have ∼70% less nos and increasing the presence of defective primordial germ cells. Our results highlight the impact that evolution has on germ granules, which should provide broader insight into processes that modify compositions and activities of other classes of biomolecular condensate.
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- Award ID(s):
- 2237390
- PAR ID:
- 10477450
- Editor(s):
- True, John
- Publisher / Repository:
- Oxford University Press on behalf of Society for Molecular Biology and Evolution
- Date Published:
- Journal Name:
- Molecular Biology and Evolution
- Volume:
- 40
- Issue:
- 8
- ISSN:
- 0737-4038
- Subject(s) / Keyword(s):
- germ granules polar granules primordial germ cells pole cells germ plasm ribonucleoproteins evolution biomolecular condensates homotypic clusters Drosophila mRNA localization nanos
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/molbev/msad174
