TY - JOUR

T1 - Functional amyloid protein FXR1 is recruited into neuronal stress granules

AU - Валина, Анна Алексеевна

AU - Белашова, Татьяна Алексеевна

AU - Юзман, Анастасия Константиновна

AU - Задорский, Сергей Павлович

AU - Сысоев, Евгений Игоревич

AU - Митькевич, Владимир Александрович

AU - Макаров, Александр Александрович

AU - Галкин, Алексей Петрович

PY - 2025/12

Y1 - 2025/12

N2 - The FXR1 protein regulates the stability and translation of a number of RNA molecules and plays an important role in the regulation of cellular processes under normal conditions and stress. In particular, this protein is known to be a negative regulator of the key proinflammatory cytokine TNF alpha. We had previously shown that FXR1 functioned in the amyloid form in neurons of the brain of jawed vertebrates. Under stress conditions, FXR1 is incorporated into stress granules in some cell lines, but such studies have not been conducted for neuronal cells. Here, we showed the ability of the FXR1 protein to form cytoplasmic granules in a neuroblastoma cell line under various types of stress. This protein colocalizes with core proteins of neuronal stress granules upon heat shock and sodium arsenite treatment. We also showed that FXR1 colocalizes with anti-amyloid antibodies OC under both normal and stress conditions. Given that stress granules are dynamic structures, we propose that amyloid FXR1-containing RNP particles interact with other stress granule proteins through weak intermolecular hydrogen bonds. Using a yeast model system, we found that FXR1 colocalizes and physically interacts with stress granule proteins such as TIA-1, FMRP, FXR2, and SFPQ. Overall, our results provide new insights into the role of the RNA-binding protein FXR1 in neuronal stress response. We believe that FXR1 inactivation in neuronal stress granules can contribute to an increase in the level of the proinflammatory cytokine TNF alpha in neurodegenerative diseases.

AB - The FXR1 protein regulates the stability and translation of a number of RNA molecules and plays an important role in the regulation of cellular processes under normal conditions and stress. In particular, this protein is known to be a negative regulator of the key proinflammatory cytokine TNF alpha. We had previously shown that FXR1 functioned in the amyloid form in neurons of the brain of jawed vertebrates. Under stress conditions, FXR1 is incorporated into stress granules in some cell lines, but such studies have not been conducted for neuronal cells. Here, we showed the ability of the FXR1 protein to form cytoplasmic granules in a neuroblastoma cell line under various types of stress. This protein colocalizes with core proteins of neuronal stress granules upon heat shock and sodium arsenite treatment. We also showed that FXR1 colocalizes with anti-amyloid antibodies OC under both normal and stress conditions. Given that stress granules are dynamic structures, we propose that amyloid FXR1-containing RNP particles interact with other stress granule proteins through weak intermolecular hydrogen bonds. Using a yeast model system, we found that FXR1 colocalizes and physically interacts with stress granule proteins such as TIA-1, FMRP, FXR2, and SFPQ. Overall, our results provide new insights into the role of the RNA-binding protein FXR1 in neuronal stress response. We believe that FXR1 inactivation in neuronal stress granules can contribute to an increase in the level of the proinflammatory cytokine TNF alpha in neurodegenerative diseases.

KW - Amyloid/metabolism

KW - Animals

KW - Arsenites/pharmacology

KW - Cell Line, Tumor

KW - Cytoplasmic Granules/metabolism

KW - Humans

KW - Neurons/metabolism

KW - RNA-Binding Proteins/metabolism

KW - Sodium Compounds/pharmacology

KW - Stress Granules/metabolism

KW - Stress, Physiological

KW - sodium arsenite

KW - neurodegenerative disease

KW - heat shock

KW - RNA-binding proteins

KW - functional amyloid

KW - FXR1

KW - TIA-1

KW - neuroinflammation

KW - stress granules

KW - FRET

UR - https://www.mendeley.com/catalogue/dcff5c99-afc7-3d1d-b9cd-e8876cd8ea1d/

U2 - 10.1080/19336896.2025.2505422

DO - 10.1080/19336896.2025.2505422

M3 - Article

C2 - 40411539

VL - 19

SP - 1

EP - 16

JO - Prion

JF - Prion

SN - 1933-6896

IS - 1

ER -