Journal Article

DZNE-2020-05954

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png More stressed out with age? Check your RNA granule aggregation.

Lechler, M. C. (First author)DZNE* ; David, D. C. (Last author)DZNE*

2017
Taylor & Francis London [u.a.]

This record in other databases:    

Please use a persistent id in citations: doi:10.1080/19336896.2017.1356559

Abstract: 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.

Keyword(s): Aging: metabolism (MeSH) ; Animals (MeSH) ; Caenorhabditis elegans: genetics (MeSH) ; Caenorhabditis elegans Proteins: metabolism (MeSH) ; Cytoplasmic Granules: metabolism (MeSH) ; Forkhead Transcription Factors: metabolism (MeSH) ; Humans (MeSH) ; Longevity (MeSH) ; Neurodegenerative Diseases: metabolism (MeSH) ; Poly(A)-Binding Protein I: metabolism (MeSH) ; Prions: metabolism (MeSH) ; Protein Aggregation, Pathological: metabolism (MeSH) ; Proteome: chemistry (MeSH) ; RNA: metabolism (MeSH) ; RNA-Binding Proteins: metabolism (MeSH) ; Stress, Physiological (MeSH) ; Transcription Factors: metabolism (MeSH) ; Caenorhabditis elegans Proteins ; Forkhead Transcription Factors ; Poly(A)-Binding Protein I ; Prions ; Proteome ; RNA-Binding Proteins ; Transcription Factors ; daf-16 protein, C elegans ; heat shock factor-1, C elegans ; RNA

---

Contributing Institute(s):

1. Protein Aggregation and Aging (AG David)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2017

---

Database coverage:
; ; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; DOAJ Seal ; IF < 5 ; JCR ; SCOPUS ; Web of Science Core Collection

---