Nat Commun. 2022 May 19;13(1):2782. doi: 10.1038/s41467-022-30066-4.

Kavya Vinayan Pushpalatha¹, Mathilde Solyga¹, Akira Nakamura^2,3, Florence Besse⁴

 

Affiliations

¹Université Côte d’Azur, CNRS, Inserm, Institut de Biologie Valrose, Nice, France.
²Department of Germline Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
³Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
⁴Université Côte d’Azur, CNRS, Inserm, Institut de Biologie Valrose, Nice, France. Florence.BESSE@univ-cotedazur.fr.

 

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.

 

PMID: 35589695
DOI: 10.1038/s41467-022-30066-4