Histone arginine demethylase JMJD6 is linked to stress granule assembly through demethylation of the stress granule–nucleating protein G3BP1
Year: 2017
Type: article
Abstract: Stress granules (SG) are membrane-less organelles that are condensates of stalled translation initiation complexes and mRNAs. SG formation is a cytoprotective response to environmental stress and results from protein interactions involving regions of low amino acid complexity and poorly defined post-translational modifications of SG components. Many RNA-binding proteins are methylated, and we previously demonstrated that the potent SG-nucleating protein G3BP1 is methylated by protein arginine methyltransferase 1 and 5 (PRMT1 and PRMT5). G3BP1 methylation represses SG formation and is reversible. Here we functionally link JMJD6 (Jumonji C domain-containing protein 6) to G3BP1 demethylation. Our findings reveal that JMJD6 is a novel SG component that interacts with G3BP1 complexes, and its expression reduces G3BP1 monomethylation and asymmetric dimethylation at three Arg residues. Knockdown of JMJD6 repressed SG formation and G3BP1 demethylation, but SG formation and G3BP1 demethylation were rescued with catalytically active but not mutant JMJD6. These results suggest that JMJD6 functions directly or indirectly as an arginine demethylase of G3BP1 that promotes SG formation.
Source: Journal of Biological Chemistry
Institution: Baylor College of Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Funders: Dan L. Duncan Cancer Center, Baylor College of Medicine, John S. Dunn Gulf Coast Consortium for Chemical Genomics, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: CONTROL OF TRANSLATION BY POLIOVIRUS PROTEINASE, Translation Regulation by Enterovirus Proteinase, CENTER FOR REPRODUCTIVE BIOLOGY RESEARCH, G3725996705, Center for Reproductive Biological Research, Developmental Biology of Neural Diseases, G5465708471, G5508324684, Translation Regulation by Enterovirus Proteinase, G7557813972, G9000013585, G9000153121, G9000240210, G9000324878, Texas Medical Center Digestive Diseases Center, Baylor College of Medicine Cancer Center - Cancer Center Support Grant
OpenAlex ID: W2760227563