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
  • [1] Chromatin changes caused by expansion of CGG repeats in fmr1 gene
    D. V. Yudkin
    N. A. Lemskaya
    I. V. Grischenko
    A. A. Dolskiy
    Molecular Biology, 2015, 49 : 179 - 184
  • [2] Chromatin changes caused by expansion of CGG repeats in fmr1 gene
    Yudkin, D. V.
    Lemskaya, N. A.
    Grischenko, I. V.
    Dolskiy, A. A.
    MOLECULAR BIOLOGY, 2015, 49 (02) : 179 - 184
  • [3] Relevance of triple CGG repeats in the FMR1 gene to ovarian reserve
    Gleicher, Norbert
    Weghofer, Andrea
    Oktay, Kutluk
    Barad, David
    REPRODUCTIVE BIOMEDICINE ONLINE, 2009, 19 (03) : 385 - 390
  • [4] CGG repeat in the FMR1 gene: size matters
    Willemsen, R.
    Levenga, J.
    Oostra, B. A.
    CLINICAL GENETICS, 2011, 80 (03) : 214 - 225
  • [5] Comparative analysis of DNA methylation in transgenic mice with unstable CGG repeats from FMR1 gene
    Alam, Mohammad Parwez
    Datta, Sonal
    Majumdar, Subeer
    Mehta, Abhishek K.
    Baskaran, Sujatha
    Gulati, Neerja
    Brahmachari, Vani
    EPIGENETICS, 2010, 5 (03) : 241 - 248
  • [6] CONSERVATION OF CGG REGION IN FMR1 GENE IN MAMMALS
    DEELEN, W
    BAKKER, C
    HALLEY, DJJ
    OOSTRA, BA
    AMERICAN JOURNAL OF MEDICAL GENETICS, 1994, 51 (04): : 513 - 516
  • [7] CGG Repeat-Induced FMR1 Silencing Depends on the Expansion Size in Human iPSCs and Neurons Carrying Unmethylated Full Mutations
    Brykczynska, Urszula
    Pecho-Vrieseling, Eline
    Thiemeyer, Anke
    Klein, Jessica
    Fruh, Isabelle
    Doll, Thierry
    Manneville, Carole
    Fuchs, Sascha
    Iazeolla, Mariavittoria
    Beibel, Martin
    Roma, Guglielmo
    Naumann, Ulrike
    Kelley, Nicholas
    Oakeley, Edward J.
    Mueller, Matthias
    Gomez-Mancilla, Baltazar
    Buhler, Marc
    Tabolacci, Elisabetta
    Chiurazzi, Pietro
    Neri, Giovanni
    Bouwmeester, Tewis
    Di Giorgio, Francesco Paolo
    Fodor, Barna D.
    STEM CELL REPORTS, 2016, 7 (06): : 1059 - 1071
  • [8] The association of FMR1 gene (CGG)n variation with idiopathic female infertility
    Grasmane, Adele
    Rots, Dmitrijs
    Vitina, Zane
    Magomedova, Valerija
    Gailite, Linda
    ARCHIVES OF MEDICAL SCIENCE, 2021, 17 (05) : 1303 - 1307
  • [9] Distribution of CGG/GCC Repeats at the FMR1 and FMR2 Genes in an Indian Population with Mental Retardation of Unknown Etiology
    Katikala, Lavanya
    Guruju, Mallikarjuna R.
    Madireddi, Sujatha
    Vallamkonda, Omsairamesh
    Vallamkonda, Nagaratna
    Persha, Amarjyothi
    Spurgeon, Anandaraj M. P. J.
    GENETIC TESTING AND MOLECULAR BIOMARKERS, 2011, 15 (04) : 281 - 284
  • [10] THE SPECTRUM OF SYNDROMIC DISORDERS ASSOCIATED WITH EXPANSION OF CGG-REPEATS IN THE FMR1 PROMOTER: PATHOGENETIC MECHANISMS AND CLINICAL SYMPTOMS
    Pereverzeva, D. S.
    Tyushkevich, S. A.
    Ulas, E., V
    Gorbachevskaya, N. L.
    ZHURNAL VYSSHEI NERVNOI DEYATELNOSTI IMENI I P PAVLOVA, 2022, 72 (03) : 293 - 316
12345