Reduced insulin/IGF-1 signaling restores the dynamic properties of key stress granule proteins during aging
| Autor: | Marie C. Lechler, Della C. David |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
metabolism [Caenorhabditis elegans Proteins] Aging Proteome RNA-binding protein Protein aggregation metabolism [Neurodegenerative Diseases] Biochemistry Poly(A)-Binding Protein I Chronic stress metabolism [Transcription Factors] Caenorhabditis elegans daf-16 protein C elegans metabolism [Forkhead Transcription Factors] RNA-Binding Proteins Forkhead Transcription Factors Neurodegenerative Diseases Cell biology Infectious Diseases metabolism [Poly(A)-Binding Protein I] metabolism [RNA] genetics [Caenorhabditis elegans] endocrine system stress granules Prions Longevity prion-like domains Biology metabolism [RNA-Binding Proteins] Cytoplasmic Granules Protein Aggregation Pathological protein aggregation 03 medical and health sciences Cellular and Molecular Neuroscience Stress granule metabolism [Protein Aggregation Pathological] Stress Physiological ddc:570 heat shock factor-1 C elegans Animals Humans metabolism [Aging] Caenorhabditis elegans Proteins Transcription factor chemistry [Proteome] Extra Views RNA Cell Biology biology.organism_classification metabolism [Cytoplasmic Granules] 030104 developmental biology Cytoplasm metabolism [Prions] Transcription Factors |
| Zdroj: | Prion Prion 11(5), 313-322 (2017). doi:10.1080/19336896.2017.1356559 |
| ISSN: | 1933-690X 1933-6896 |
| Popis: | Low complexity (LC) prion-like domains are over-represented among RNA-binding proteins (RBPs) and contribute to the dynamic nature of RNA granules. Importantly, several neurodegenerative diseases are characterized by cytoplasmic “solid” aggregates formed by mainly nuclear RBPs harboring LC prion-like domains. Although RBP aggregation in disease has been extensively characterized, it remains unknown how the process of aging disturbs RBP dynamics. Our recent study revealed that RNA granule components including 2 key stress granule RBPs with LC prion-like domains, PAB-1 and TIAR-2, aggregate in aged Caenorhabditis elegans in the absence of disease. Here we present new evidence showing that sustained stress granule formation triggers RBP aggregation. In addition, we demonstrate that mild chronic stress during aging promotes mislocalization of nuclear RBPs. We discuss the consequences of aberrant interactions between age-related RBP aggregation and disease-associated RBP aggregation. In particular, we show that FUST-1 and PAB-1 co-localize in aberrant cytoplasmic accumulations. Significantly, long-lived animals with reduced insulin/IGF-1 signaling abrogate stress granule RBP aggregation through activation of the transcription factors HSF-1 and DAF-16. We evaluate the different mechanisms that could maintain dynamic stress granules. Together these findings highlight how changes with age could contribute to pathogenesis in neurodegenerative diseases and disruption of RNA homeostasis. |
| Databáze: | OpenAIRE |
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