Molecular Chaperones Regulating the Dynamics, Composition and Functionality of RNP Granules: Implications for Age-Related Diseases

The maturation, storage and degradation of RNAs occur in RNA-protein membrane-less assemblies that have properties of liquid droplets and arise from the surrounding aqueous cytoplasm or nucleoplasm through a process known as liquid-liquid phase separation. In healthy cells, ribonucleoprotein (RNP) granules are highly dynamic compartments. In contrast, in aging cells or due to environmental stresses or genetic mutations, RNP granules, in particular stress granules (SGs), convert into solid, aggregate-like inclusions. The accumulation of these RNA-protein inclusions is linked to an increasing number of age-related neurodegenerative diseases, such as amyotrophic lateral sclerosis and frontotemporal dementia. Thus, a detailed understanding of the molecular causes underlying the conversion of liquid-like RNPs into aggregates and the identification of the cellular players that can prevent this conversion may represent a valid approach to combat these diseases.