CGG repeats in the human FMR1 gene regulate mRNA localization and cellular stress in developing neurons
Year: 2024
Type: article
Abstract: The human genome has many short tandem repeats, yet the normal functions of these repeats are unclear. The 5' untranslated region (UTR) of the fragile X messenger ribonucleoprotein 1 (FMR1) gene contains polymorphic CGG repeats, the length of which has differing effects on FMR1 expression and human health, including the neurodevelopmental disorder fragile X syndrome. We deleted the CGG repeats in the FMR1 gene (0CGG) in human stem cells and examined the effects on differentiated neurons. 0CGG neurons have altered subcellular localization of FMR1 mRNA and protein, and differential expression of cellular stress proteins compared with neurons with normal repeats (31CGG). In addition, 0CGG neurons have altered responses to glucocorticoid receptor (GR) activation, including FMR1 mRNA localization, GR chaperone HSP90α expression, GR localization, and cellular stress protein levels. Therefore, the CGG repeats in the FMR1 gene are important for the homeostatic responses of neurons to stress signals.
Source: Cell Reports
Institution: University of Wisconsin–Madison
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,460
Funders: U.S. Department of Defense, FRAXA Research Foundation, Brain Research Foundation, Simons Foundation, Wisconsin Alumni Research Foundation, John Merck Fund, Waisman Center, Autism Science Foundation, Eagles Autism Foundation, National Institutes of Health, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Identification of FMRP targets in human cortical neurons, The role of RNA binding protein in FXR1P in interneurons, G1517152792, Waisman Intellectual and Developmental Disabilities Research Center, Integration of Experience-Induced Gene Expression and Circuit Functions, G4119534169, G5741685586, G5850682332, G7388523079, The Role of MDM2 in FMRP regulation of neuronal development, Interrogate FMRP functions in primate brain development, Waisman Center Intellectual and Developmental Disabilities Research Center, Characterization of Fragile X Syndrome 3D Cortical Organoids
OpenAlex ID: W4399588663