RNP components condense into repressive RNP granules in the aging brain

Kavya Vinayan Pushpalatha, Mathilde Solyga, Akira Nakamura and Florence Besse ()
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Kavya Vinayan Pushpalatha: Université Côte d’Azur, CNRS, Inserm, Institut de Biologie Valrose
Mathilde Solyga: Université Côte d’Azur, CNRS, Inserm, Institut de Biologie Valrose
Akira Nakamura: Kumamoto University
Florence Besse: Université Côte d’Azur, CNRS, Inserm, Institut de Biologie Valrose

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-30066-4

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