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RNP components condense into repressive RNP granules in the aging brain

Author

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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
    Kumamoto University)

  • Florence Besse

    (Université Côte d’Azur, CNRS, Inserm, Institut de Biologie Valrose)

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.

Suggested Citation

  • Kavya Vinayan Pushpalatha & Mathilde Solyga & Akira Nakamura & Florence Besse, 2022. "RNP components condense into repressive RNP granules in the aging brain," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30066-4
    DOI: 10.1038/s41467-022-30066-4
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    References listed on IDEAS

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    1. Jeshlee Vijayakumar & Charlène Perrois & Marjorie Heim & Luc Bousset & Simon Alberti & Florence Besse, 2019. "The prion-like domain of Drosophila Imp promotes axonal transport of RNP granules in vivo," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    2. Karl E. Bauer & Niklas Bargenda & Rico Schieweck & Christin Illig & Inmaculada Segura & Max Harner & Michael A. Kiebler, 2022. "RNA supply drives physiological granule assembly in neurons," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
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    Cited by:

    1. Karl E. Bauer & Niklas Bargenda & Rico Schieweck & Christin Illig & Inmaculada Segura & Max Harner & Michael A. Kiebler, 2022. "RNA supply drives physiological granule assembly in neurons," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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