Cytoplasmic RNP condensates enriched in mRNAs and proteins are found in various cell types and associated with both buffering and regulatory functions. While a clear link has been established between accumulation of aberrant RNP aggregates and progression of aging-related neurodegenerative diseases, the impact of physiological aging on neuronal RNP condensates has never been explored. Through high-resolution imaging, we uncover that RNP components progressively cluster into large yet dynamic granules in the aging Drosophila brain. We further show that age-dependent clustering is caused by an increase in the stoichiometry of the conserved helicase Me31B/DDX6, and requires PKA kinase activity. Finally, our functional analysis reveals that mRNA species recruited to RNP condensates upon aging exhibit age-dependent translational repression, indicating that co-clustering of selected mRNAs and translation regulators into repressive condensates may contribute to the specific post-transcriptional changes in gene expression observed in the course of aging.
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http://dx.doi.org/10.1038/s41467-022-30066-4 | DOI Listing |
Curr Biol
January 2025
Department of Developmental Biology and Cancer Research, The Hebrew University of Jerusalem Faculty of Medicine, Ein-Kerem Campus, Jerusalem 9112102, Israel; Institute for Medical Research, Israel-Canada (IMRIC), Ein-Kerem Campus, Jerusalem 9112102, Israel. Electronic address:
Vertebrate oocyte polarity has been observed for two centuries and is essential for embryonic axis formation and germline specification, yet its underlying mechanisms remain unknown. In oocyte polarization, critical RNA-protein (RNP) granules delivered to the oocyte's vegetal pole are stored by the Balbiani body (Bb), a membraneless organelle conserved across species from insects to humans. However, the mechanisms of Bb formation are still unclear.
View Article and Find Full Text PDFMol Cell
December 2024
Biotechnology Center, Center for Molecular and Cellular Bioengineering, TU Dresden, Dresden 01307 Saxony, Germany; Cluster of Excellence Physics of Life, TU Dresden, Dresden 01307 Saxony, Germany. Electronic address:
Ribonucleoprotein (RNP) granules have been linked to translation regulation and disease, but their assembly and regulatory mechanisms are not well understood. Here, we show that the RNA-binding protein G3BP1 preferentially interacts with unfolded RNA, driving the assembly of RNP granule-like condensates that establish RNA-RNA interactions. These RNA-RNA interactions limit the mobility and translatability of sequestered mRNAs and stabilize the condensates.
View Article and Find Full Text PDFMol Cell
November 2024
Department of Biochemistry, University of Colorado Boulder, Boulder, CO 80309, USA; Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address:
Ribonucleoprotein (RNP) granules are biomolecular condensates requiring RNA and proteins to assemble. Stress granules are RNP granules formed upon increases in non-translating messenger ribonucleoprotein particles (mRNPs) during stress. G3BP1 and G3BP2 proteins are proposed to assemble stress granules through multivalent crosslinking of RNPs.
View Article and Find Full Text PDFCell Stress
October 2024
University Medical Center Göttingen, Department of Otolaryngology-Head and Neck Surgery, InnerEarLab Göttingen Germany.
Stress granules (SGs) are highly dynamic micromolecular membraneless condensates that generate in cells subjected to stress. Formed from pools of untranslating messenger ribonucleoproteins (RNP), SGs dynamics constitute vital processes essential for cell survival. Here, we investigate whether established cytotoxic agents, such as the platinum-based chemotherapeutic agent cisplatin and the aminoglycoside antibiotic gentamicin, elicit SG formation in the House Ear Institute-Organ of Corti-1 (HEI-OC1) auditory cell line, H4 human neuroglioma cells and HEK-293T human embryonic kidney cells.
View Article and Find Full Text PDFEMBO Rep
December 2024
Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose, Nice, France.
Aging is characterized by a decline in various biological functions that is associated with changes in gene expression programs. Recent transcriptome-wide integrative studies in diverse organisms and tissues have revealed a gradual uncoupling between RNA and protein levels with aging, which highlights the importance of post-transcriptional regulatory processes. Here, we provide an overview of multi-omics analyses that show the progressive uncorrelation of transcriptomes and proteomes during the course of healthy aging.
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