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 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.
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http://dx.doi.org/10.7554/eLife.52896 | DOI Listing |
PLoS Genet
January 2025
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, United States of America.
De novo mutations in the RNA binding protein DDX3X cause neurodevelopmental disorders including DDX3X syndrome and autism spectrum disorder. Amongst ~200 mutations identified to date, half are missense. While DDX3X loss of function is known to impair neural cell fate, how the landscape of missense mutations impacts neurodevelopment is almost entirely unknown.
View Article and Find Full Text PDFAnal Chem
January 2025
Institute of Physical Science and Information Technology, Information Materials and Intelligent Sensing Laboratory of Anhui Province, Key Laboratory of Structure and Functional Regulation of Hybrid Materials of Ministry of Education, Anhui University, Hefei, Anhui 230601, China.
Real-time monitoring of the dynamics of cytosolic RNA-protein condensates, termed stress granules (SGs), is vital for understanding their biological roles in stress response and related disease treatment but is challenging due to the lack of simple and accurate methods. Compared with protein visualization that requires complex transfection procedures, direct RNA labeling offers an ideal alternative for tracking SG dynamics in living cells. Here, we propose a novel molecular design strategy to construct a near-infrared RNA-specific fluorescent probe () for tracking SGs in living cells.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
January 2025
Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica Ranwel Caputto. Córdoba, Argentina.
Purpose: Stress granules (SGs) are cytoplasmic biocondensates formed in response to various cellular stressors, contributing to cell survival. Although implicated in diverse pathologies, their role in retinal degeneration (RD) remains unclear. We aimed to investigate SG formation in the retina and its induction by excessive LED light in an RD model.
View Article and Find Full Text PDFClin Exp Med
January 2025
The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
Upon stimulation and activation, mast cells (MCs) release soluble mediators, including histamine, proteases, and cytokines. These mediators are often stored within cytoplasmic granules in MCs and may be released in a granulated form. The secretion of cytokines and chemokines occurs within hours following activation, with the potential to result in chronic inflammation.
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