RNA granules in neuronal plasticity and disease

• Published in: Trends in neurosciences (Regular ed.) Vol. 46; no. 7; pp. 525 - 538
• Main Authors: Bauer, Karl E., de Queiroz, Bruna R., Kiebler, Michael A., Besse, Florence
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-07-2023
• Subjects: aging; biological condensate; Cytoplasmic Granules - metabolism; Cytoplasmic Ribonucleoprotein Granules; Humans; neurodegenerative diseases; Neuronal Plasticity - physiology; Neurons - metabolism; phase separation; RNA - metabolism; RNA-binding proteins; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; synaptic plasticity; neurodegenerative diseases; phase separation; biological condensate; RNA-binding proteins; aging; synaptic plasticity
• ISSN: 0166-2236; 1878-108X
• DOI: 10.1016/j.tins.2023.04.004

Selected RNA-binding proteins self-assemble together with their cognate RNAs in a dynamic and controlled manner into neuronal RNA granules.These RNA condensates represent membraneless organelles that undergo selective remodeling, including disassembly, in response to synaptic activation.This activity-dependent remodeling releases granule-associated transcripts from translational repression, initiating translation at the synapse.Both neuronal maturation and physiological aging change the condensation properties of neuronal RNA granules.Repeated cycles of assembly/disassembly affect the long-term properties of RNA granules, providing a molecular framework for processes occurring during synaptic plasticity. Pathological aging instead triggers increased irreversibility up to the formation of cellular inclusions.
RNA granules are dynamic entities controlling the spatiotemporal distribution and translation of RNA molecules. In neurons, a variety of RNA granules exist both in the soma and in cellular processes. They contain transcripts encoding signaling and synaptic proteins as well as RNA-binding proteins causally linked to several neurological disorders. In this review, we highlight that neuronal RNA granules exhibit properties of biomolecular condensates that are regulated upon maturation and physiological aging and how they are reversibly remodeled in response to neuronal activity to control local protein synthesis and ultimately synaptic plasticity. Moreover, we propose a framework of how neuronal RNA granules mature over time in healthy conditions and how they transition into pathological inclusions in the context of late-onset neurodegenerative diseases.