Protein-based condensation mechanisms drive the assembly of RNA-rich P granules
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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-06-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/63698 |
| _version_ | 1818025117021634560 |
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| author | Helen Schmidt Andrea Putnam Dominique Rasoloson Geraldine Seydoux |
| author_facet | Helen Schmidt Andrea Putnam Dominique Rasoloson Geraldine Seydoux |
| author_sort | Helen Schmidt |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T04:11:00Z |
| format | Article |
| id | doaj.art-b9385f04abef4019b8667701e6cb0f3a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:11:00Z |
| publishDate | 2021-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b9385f04abef4019b8667701e6cb0f3a2022-12-22T02:02:45ZengeLife Sciences Publications LtdeLife2050-084X2021-06-011010.7554/eLife.63698Protein-based condensation mechanisms drive the assembly of RNA-rich P granulesHelen Schmidt0https://orcid.org/0000-0002-3449-2790Andrea Putnam1https://orcid.org/0000-0001-7985-142XDominique Rasoloson2https://orcid.org/0000-0003-2210-1569Geraldine Seydoux3https://orcid.org/0000-0001-8257-0493HHMI and Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United StatesHHMI and Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United StatesHHMI and Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United StatesHHMI and Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United StatesGerm 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.https://elifesciences.org/articles/63698RNA granuleintrinsically disordered proteinphase separationgerm plasmP granule |
| spellingShingle | Helen Schmidt Andrea Putnam Dominique Rasoloson Geraldine Seydoux Protein-based condensation mechanisms drive the assembly of RNA-rich P granules eLife RNA granule intrinsically disordered protein phase separation germ plasm P granule |
| title | Protein-based condensation mechanisms drive the assembly of RNA-rich P granules |
| title_full | Protein-based condensation mechanisms drive the assembly of RNA-rich P granules |
| title_fullStr | Protein-based condensation mechanisms drive the assembly of RNA-rich P granules |
| title_full_unstemmed | Protein-based condensation mechanisms drive the assembly of RNA-rich P granules |
| title_short | Protein-based condensation mechanisms drive the assembly of RNA-rich P granules |
| title_sort | protein based condensation mechanisms drive the assembly of rna rich p granules |
| topic | RNA granule intrinsically disordered protein phase separation germ plasm P granule |
| url | https://elifesciences.org/articles/63698 |
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