@article{e9be0785a39c40a5a8fa82c14331ffd5,
title = "Recruitment of mRNAs to P granules by condensation with intrinsically-disordered proteins",
abstract = "RNA granules are protein/RNA condensates. How specific mRNAs are recruited to cytoplasmic RNA granules is not known. Here, we characterize the transcriptome and assembly of P granules, RNA granules in the C. elegans germ plasm. We find that P granules recruit mRNAs by condensation with the disordered protein MEG-3. MEG-3 traps mRNAs into non-dynamic condensates in vitro and binds to ~500 mRNAs in vivo in a sequence-independent manner that favors embryonic mRNAs with low ribosome coverage. Translational stress causes additional mRNAs to localize to P granules and translational activation correlates with P granule exit for two mRNAs coding for germ cell fate regulators. Localization to P granules is not required for translational repression but is required to enrich mRNAs in the germ lineage for robust germline development. Our observations reveal similarities between P granules and stress granules and identify intrinsically-disordered proteins as drivers of RNA condensation during P granule assembly.",
author = "Lee, {Chih Yung S.} and Andrea Putnam and Tu Lu and He, {Shuai Xin} and Ouyang, {John Paul T.} and Geraldine Seydoux",
note = "Funding Information: We thank the Johns Hopkins Neuroscience Research Multiphoton Imaging Core (NS050274) and the Johns Hopkins Integrated Imaging Center (S10OD023548) for excellent microscopy support. We thank the Lavis lab for Halo Ligand JF646, the Griffin lab for MEG-3::Halo strain, the Nathans lab for the OLLAS antibody, Addgene for TEV protease from the Waugh lab, and Colin Wu for assistance with ribosome profiling experiments. We especially thank Dr. Sijung Yun (Yotta Biomed) for his assistance with data analysis. We also thank the Baltimore Worm club and the Seydoux lab for many helpful discussions. This work was supported by the National Institutes of Health (NIH) (grant number R37 HD37047). JPTO was supported by the JHU SOM Biochemistry, Cellular, and Molecular Biology NIH training grant (T32 GM007445). GS is an investigator of the Howard Hughes Medical Institute. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). Data acquired using the Zeiss LSM 800 Confocal reported in this publication was supported by Office of the Director, NIH (OD) of the National Institutes of Health (award number S10OD016374). Funding Information: We thank the Johns Hopkins Neuroscience Research Multiphoton Imaging Core (NS050274) and the Johns Hopkins Integrated Imaging Center (S10OD023548) for excellent microscopy support. We thank the Lavis lab for Halo Ligand JF646, the Griffin lab for MEG-3::Halo strain, the Nathans lab for the OLLAS antibody, Addgene for TEV protease from the Waugh lab, and Colin Wu for assistance with ribosome profiling experiments. We especially thank Dr. Sijung Yun (Yotta Biomed) for his assistance with data analysis. We also thank the Baltimore Worm club and the Seydoux lab for many helpful discussions. This work was supported by the National Institutes of Health (NIH) (grant number R37 HD37047). JPTO was supported by the JHU SOM Biochemistry, Cellular, and Molecular Biology NIH training grant (T32 GM007445). GS is an investigator of the Howard Hughes Medical Institute. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). Data acquired using the Zeiss LSM 800 Confocal reported in this publication was supported by Office of the Director, NIH (OD) of the National Institutes of Health (award number S10OD016374).. National Institutes of Health. R37 HD37047. Geraldine Seydoux. Howard Hughes Medical Institute. Geraldine Seydoux. National Institutes of Health. T32 GM007445. John Paul T Ouyang. Publisher Copyright: {\textcopyright} Lee et al.",
year = "2020",
month = jan,
doi = "10.7554/eLife.52896",
language = "English (US)",
volume = "9",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}