Publication Date:
2022-05-26
Description:
© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Begovich, K., Vu, A. Q., Yeo, G., & Wilhelm, J. E. Conserved metabolite regulation of stress granule assembly via AdoMet. Journal of Cell Biology, 219(8), (2020): e201904141, doi:10.1083/jcb.201904141.
Description:
Stress granules (SGs) are evolutionarily conserved condensates of ribonucleoproteins that assemble in response to metabolic stresses. Because aberrant SG formation is associated with amyotrophic lateral sclerosis (ALS), understanding the connection between metabolic activity and SG composition can provide therapeutic insights into neurodegeneration. Here, we identify 17 metabolic enzymes recruited to yeast SGs in response to physiological growth stress. Furthermore, the product of one of these enzymes, AdoMet, is a regulator of SG assembly and composition. Decreases in AdoMet levels increase SG formation, while chronic elevation of AdoMet produces SG remnants lacking proteins associated with the 5′ end of transcripts. Interestingly, acute elevation of AdoMet blocks SG formation in yeast and motor neurons. Treatment of ALS-derived motor neurons with AdoMet also suppresses the formation of TDP-43–positive SGs, a hallmark of ALS. Together, these results argue that AdoMet is an evolutionarily conserved regulator of SG composition and assembly with therapeutic potential in neurodegeneration.
Description:
Work from the Wilhelm laboratory was supported by a grant to J.E. Wilhelm from the Collaborative Innovation Awards program of Howard Hughes Medical Institute and the James Wilhelm Memorial Fund. K. Begovich is a Howard Hughes Medical Institute Gilliam Fellow. Work from the Yeo laboratory was supported by grants to G. Yeo from the National Institutes of Health (HG004659), Target ALS (20193440), and the ALS Association (272 and 438).
Repository Name:
Woods Hole Open Access Server
Type:
Article
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