Cytoplasmic granule formation by FUS‐R495X is attributable to arginine methylation in all Gly‐rich, RGG1 and RGG2 domains
Many mutations in the fused in sarcoma (FUS) gene have been identified as genetic causative factors of amyotrophic lateral sclerosis (ALS). As a certain number of mutants form aberrant cytoplasmic granules under specific conditions, granule forming ability of FUS is believed to be linked to the path...
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Published in | Genes to cells : devoted to molecular & cellular mechanisms Vol. 26; no. 3; pp. 190 - 197 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
England
Wiley Subscription Services, Inc
01.03.2021
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Subjects | |
Online Access | Get full text |
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Summary: | Many mutations in the fused in sarcoma (FUS) gene have been identified as genetic causative factors of amyotrophic lateral sclerosis (ALS). As a certain number of mutants form aberrant cytoplasmic granules under specific conditions, granule forming ability of FUS is believed to be linked to the pathogenesis of ALS. However, molecular mechanisms underlying this property remain unclear. An ALS‐linked FUS mutant, R495X, shows extensive cytoplasmic localization and forms granules in neurons. In the present study, using R495X domain deletion constructs, we showed that deletion of any of Gly‐rich, RGG1 or RGG2 significantly suppressed granule formation. Furthermore, when neurons expressing EGFP‐R495X were treated with an arginine methylation inhibitor, the number of cells displaying R495X granules was significantly reduced. When FLAG‐tagged arginine N‐methyltransferase 8 (PRMT8) was co‐expressed with EGFP‐R495X to facilitate its methylation, the number of cells with granules was significantly increased. Collectively, these findings suggest that cytoplasmic granule formation by R495X is attributable to the arginine methylation in all Gly‐rich, RGG1 and RGG2 domains.
Fused in sarcoma (FUS) is one of the causative factors of amyotrophic lateral sclerosis (ALS). An ALS‐linked mutant, R495X, forms cytoplasmic granules in neurons. We revealed that the granule formation of R495X is attributable to the methylation in all Gly‐rich, RGG1 and RGG2 domains. |
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Bibliography: | Communicated by: Kozo Kaibuchi ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1356-9597 1365-2443 |
DOI: | 10.1111/gtc.12827 |