Stress Granules Control Alzheimer's Gene Transcripts and Neuronal Proteostasis
06-01-2023“Determining the mechanism underlying RNA sequestration in [stress granules] [...] could represent a key goal in the discovery and development of suitable [Alzheimer’s disease] biomarkers and therapies.”
BUFFALO, NY- June 1, 2023 – A new research paper was published on the cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 10, entitled, “Stress granules sequester Alzheimer’s disease-associated gene transcripts and regulate disease-related neuronal proteostasis.”
Environmental and physiological stresses can accelerate Alzheimer’s disease (AD) pathogenesis. Under stress, a cytoplasmic membraneless structure termed a stress granule (SG) is formed and is associated with various neurodegenerative disorders, including AD. SGs contain translationally arrested mRNAs, suggesting that impaired RNA metabolism in neurons causes AD progression; however, the underlying mechanism remains unclear.
In this new study, researchers Kaoru Sato, Ken-ichi Takayama and Satoshi Inoue from Tokyo Metropolitan Institute for Geriatrics and Gerontology identified numerous mRNAs and long non-coding RNAs that are directly targeted by the SG core proteins G3BP1 and G3BP2.
“In this study, we conducted a genome-wide investigation of the G3BP1- and G3BP2-bound RNAs using enhanced cross-linking and immunoprecipitation-sequencing (eCLIP-seq) in the human neuroblastoma (NB) cell line SH-SY5Y.”
G3BP1 and G3BP2 redundantly target RNAs before and after stress conditions. The researchers further identified RNAs within SGs, wherein AD-associated gene transcripts accumulated, suggesting that SGs can directly regulate AD development. Furthermore, gene-network analysis revealed a possible link between the sequestration of RNAs by SGs and the impairment of protein neurohomeostasis in AD brains.
“Together, our study provides a comprehensive RNA regulatory mechanism involving SGs, which could be targeted therapeutically to slow AD progression mediated by SGs.”
Read the full study: DOI: https://doi.org/10.18632/aging.204737
Corresponding Author: Satoshi Inoue - sinoue@tmig.or.jp
Keywords: stress granule, RNP granule, eCLIP-seq, G3BP, Alzheimer’s disease
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About Aging-US:
Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.
Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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