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

  • Daniel Mateju
  • Laura Mediani
  • Federica F. Morelli
  • Simon AlbertiEmail author
  • Serena CarraEmail author
Part of the Heat Shock Proteins book series (HESP, volume 14)


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.

In this book chapter, we summarize the current knowledge about stress granule formation. We focus on recent findings demonstrating that liquid-like SGs can sequester aggregation-prone misfolded proteins with detrimental consequences for SG dynamics and functionality. We further discuss a specific protein quality control process, referred to as granulostasis, which prevents the accumulation of misfolding-prone proteins in SGs, thereby maintaining the physiological state of SGs and ensuring timely SG disassembly.


Membrane-less compartments Molecular chaperones and co-chaperones Neurodegenerative diseases Phase transition Protein aggregation Stress granules 



Alzheimer’s disease


amyotrophic lateral sclerosis


Bcl-2 associated athanogenes


chaperonin-containing t-complex polypeptide 1/TCP-1 ring complex


carboxyl terminus of Hsc70-interacting protein


frontotemporal dementia


fused in sarcoma


Huntington’s disease


heterogeneous nuclear ribonucleoprotein A1


heat shock proteins


inclusion body myopathy


intrinsically disordered protein


intrinsically disordered region


microtubule-associated protein 1A/1B-light chain 3


low-complexity sequences


mammalian target of rapamycin


nucleotide-exchange factors


Parkinson’s disease


promyelocytic leukemia protein


protein quality control


receptor for activated C kinase 1


repeat-associated non-ATG


RNA-binding protein


ribonucleoprotein particle


stress granule


superoxide dismutase 1


sequestosome 1


TAR DNA-binding protein 43


T-cell intracellular antigen 1


TNF receptor associated factor



S.C. is grateful to AriSLA, The Italian Ministry of Foreign Affair and International Cooperation and the Cariplo Foundation for financial support. S.C. and S.A. acknowledge EU Joint Programme – Neurodegenerative Disease Research (JPND) project for financial support. The project is supported through funding organisations under the aegis of JPND ( This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No 643417. S.A. acknowledges funding from the Max Planck Society.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Max Planck Institute of Molecular Cell Biology and GeneticsDresdenGermany
  2. 2.Department of Biomedical, Metabolic and Neural Sciences, Center for Neuroscience and NeurotechnologyUniversity of Modena and Reggio EmiliaModenaItaly

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