CGG repeats in the human FMR1 gene regulate mRNA localization and cellular stress in developing neurons

被引：2
|
作者：
Sirois, Carissa L. [1 ,2 ]
Guo, Yu [1 ,2 ]
Li, Meng [1 ,2 ,5 ]
Wolkoff, Natalie E. [1 ,2 ]
Korabelnikov, Tomer [1 ,2 ]
Sandoval, Soraya [1 ,2 ,3 ]
Lee, Jiyoun [1 ,2 ,3 ]
Shen, Minjie [1 ,2 ,6 ,7 ]
Contractor, Amaya [1 ,2 ]
Sousa, Andre M. M. [1 ,2 ]
Bhattacharyya, Anita [1 ,4 ]
Zhao, Xinyu [1 ,2 ]
机构：
[1] Univ Wisconsin Madison, Waisman Ctr, Madison, WI 53705 USA
[2] Univ Wisconsin Madison, Dept Neurosci, Sch Med & Publ Hlth, Madison, WI 53705 USA
[3] Univ Wisconsin Madison, Neurosci Training Program, Madison, WI 53705 USA
[4] Univ Wisconsin Madison, Dept Cell & Regenerat Biol, Sch Med & Publ Hlth, Madison, WI 53705 USA
[5] Xuzhou Med Univ, Res Ctr Biochem & Mol Biol, Jiangsu Key Lab Brain Dis & Bioinformat, Xuzhou 221000, Peoples R China
[6] Fudan Univ, MOE Frontiers Ctr Brain Sci, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China
[7] Fudan Univ, Inst Brain Sci, Shanghai 200032, Peoples R China
来源：
CELL REPORTS | 2024年 / 43卷 / 06期
基金：
美国国家卫生研究院;
关键词：
FRAGILE-X-SYNDROME; MENTAL-RETARDATION PROTEIN; GLUCOCORTICOID-RECEPTOR; G-QUADRUPLEX; TRANSLATIONAL REGULATION; EXPRESSION; SEQUENCE; BETA; FORM; PHENOTYPE;
D O I：
10.1016/j.celrep.2024.114330
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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 HSP90 a 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.
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页数：28
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