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.
引用
收藏
页数：28
相关论文
共 50 条
  • [21] Reduced RNA expression of the FMR1 gene in women with low (CGGn<26) repeats
    Wang, Qi
    Barad, David H.
    Darmon, Sarah K.
    Kushnir, Vitaly A.
    Wu, Yan-Guang
    Lazzaroni-Tealdi, Emanuela
    Zhang, Lin
    Albertini, David F.
    Gleicher, Norbert
    PLOS ONE, 2018, 13 (12):
  • [22] CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons
    Yifan Zhou
    Daman Kumari
    Nicholas Sciascia
    Karen Usdin
    Molecular Autism, 7
  • [23] Molecular diagnosis of fragile X syndrome and distribution of CGG repeats in the FMR-1 gene in Taiwanese
    Wang, YC
    Li, C
    Lin, ML
    Lin, WH
    Li, SY
    JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION, 2000, 99 (05) : 402 - 407
  • [24] PGT-M for Premature Ovarian Failure Related to CGG Repeat Expansion of the FMR1 Gene
    Persico, Tiziana
    Tranquillo, Maria Lucrezia
    Seracchioli, Renato
    Zuccarello, Daniela
    Sorrentino, Ugo
    GENES, 2024, 15 (01)
  • [25] Cloning, characterization and properties of plasmids containing CGG triplet repeats from the FMR-1 gene
    Shimizu, M
    Gellibolian, R
    Oostra, BA
    Wells, RD
    JOURNAL OF MOLECULAR BIOLOGY, 1996, 258 (04) : 614 - 626
  • [26] CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons
    Zhou, Yifan
    Kumari, Daman
    Sciascia, Nicholas
    Usdin, Karen
    MOLECULAR AUTISM, 2016, 7 : 1 - 13
  • [27] FIRING PROPERTY OF INFERIOR COLLICULUS NEURONS AFFECTED BY FMR1 GENE MUTATION
    Brittany Mott
    SUN Wei
    Journal of Otology, 2014, 9 (02) : 86 - 90
  • [28] FMR1 expression in human granulosa cells increases with exon 1 CGG repeat length depending on ovarian reserve
    Rehnitz, Julia
    Alcoba, Diego D.
    Brum, Ilma S.
    Dietrich, Jens E.
    Youness, Berthe
    Hinderhofer, Katrin
    Messmer, Birgitta
    Freis, Alexander
    Strowitzki, Thomas
    Germeyer, Ariane
    REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY, 2018, 16
  • [29] Validation of a commercially available test that enables the quantification of the numbers of CGG trinucleotide repeat expansion in FMR1 gene
    Lim, Grace X. Y.
    Yeo, Minli
    Koh, Yvonne Y.
    Winarni, Tri Indah
    Rajan-Babu, Indhu-Shree
    Chong, Samuel S.
    Faradz, Sultana M. H.
    Guan, Ming
    PLOS ONE, 2017, 12 (03):
  • [30] Reduction of Fmr1 mRNA Levels Rescues Pathological Features in Cortical Neurons in a Model of FXTAS
    Drozd, Malgorzata
    Delhaye, Sebastien
    Maurin, Thomas
    Castagnola, Sara
    Grossi, Mauro
    Brau, Frederic
    Jarjat, Marielle
    Willemsen, Rob
    Capovilla, Maria
    Hukema, Renate K.
    Lalli, Enzo
    Bardoni, Barbara
    MOLECULAR THERAPY-NUCLEIC ACIDS, 2019, 18 : 546 - 553
12345