Molecular Functions of the Mammalian Fragile X Mental Retardation Protein: Insights Into Mental Retardation and Synaptic Plasticity

2013 ◽  
Author(s):  
Claudia Bagni ◽  
Eric Klann
Keyword(s):  
Mental Retardation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Fragile X ◽  
Rna Binding Protein ◽  
Fragile X Mental Retardation ◽  
The Family ◽  
Mental Retardation Protein ◽  
The Brain

Chapter 8 discusses how Fragile X syndrome (FXS) is caused by the absence of the RNA-binding protein fragile X mental retardation protein (FMRP). FMRP is highly expressed in the brain and gonads, the two organs mainly affected in patients with the syndrome. Functionally, FMRP belongs to the family of RNA-binding proteins, shuttling from the nucleus to the cytoplasm, and, as shown for other RNA-binding proteins, forms large messenger ribonucleoparticles.

scholarly journals The RNA-binding fragile-X mental retardation protein and its role beyond the brain

2020 ◽  
Vol 12 (4) ◽  
pp. 903-916 ◽  
Author(s):  
Cassandra Malecki ◽  
Brett D. Hambly ◽  
Richmond W. Jeremy ◽  
Elizabeth N. Robertson
Keyword(s):  
Mental Retardation ◽  
Rna Binding ◽  
Fragile X ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein ◽  
The Brain

scholarly journals Fragile X Mental Retardation Protein (FMRP) Binds Specifically to the Brain Cytoplasmic RNAs BC1/BC200 via a Novel RNA-binding Motif

2005 ◽  
Vol 280 (39) ◽  
pp. 33403-33410 ◽  
Author(s):  
Francesca Zalfa ◽  
Salvatore Adinolfi ◽  
Ilaria Napoli ◽  
Eva Kühn-Hölsken ◽  
Henning Urlaub ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Rna Binding ◽  
Fragile X ◽  
Binding Motif ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein ◽  
Cytoplasmic Rnas ◽  
The Brain

scholarly journals Expression of fragile X mental retardation protein and Fmr1 mRNA during folliculogenesis in the rat

Reproduction ◽  
2013 ◽  
Vol 145 (4) ◽  
pp. 335-343 ◽  
Author(s):  
Ianina Ferder ◽  
Fernanda Parborell ◽  
Victoria Sundblad ◽  
Violeta Chiauzzi ◽  
Karina Gómez ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Fragile X ◽  
Expression Patterns ◽  
Follicular Development ◽  
Mrna Levels ◽  
Germline Development ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein

Fragile X mental retardation protein (FMRP) belongs to a small family of RNA-binding proteins. Its absence or inactivity is responsible for fragile X syndrome, the most common cause of inherited mental retardation. Despite its ubiquitous expression, FMRP function and expression remain almost understudied in non-neuronal tissues, though previous studies on germline development during oogenesis may suggest a special function of this protein also in ovarian tissue. In addition, the well-documented association ofFMR1premutation state with fragile X-related premature ovarian insufficiency adds interest to the role of FMRP in ovarian physiology. The aim of the present work was to investigate the expression ofFmr1mRNA and its protein, FMRP, at different stages of rat follicular development. By immunohistochemical studies we demonstrated FMRP expression in granulosa, theca and germ cells in all stages of follicular development. In addition, changes inFmr1expression, both at the protein and mRNA levels, were observed. FMRP levels increased upon follicular development while preantral and early antral follicles presented similar levels ofFmr1transcripts with decreased expression in preovulatory follicles. These observations suggest thatFmr1expression in the ovary is regulated at different and perhaps independent levels. In addition, our results show expression of at least four different isoforms of FMRP during all stages of follicular growth with expression patterns that differ from those observed in brain and testis. Our study shows a regulated expression ofFmr1, both at mRNA and protein levels, during rat follicular development.

scholarly journals Kinase pathway inhibition restores PSD95 induction in neurons lacking fragile X mental retardation protein

2019 ◽  
pp. 201812056
Author(s):  
Ying Yang ◽  
Yang Geng ◽  
Dongyun Jiang ◽  
Lin Ning ◽  
Hyung Joon Kim ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mental Retardation ◽  
Rna Binding ◽  
Fragile X ◽  
Alternative Pathways ◽  
Fragile X Mental Retardation ◽  
Mrna Targets ◽  
Mental Retardation Protein ◽  
Pathway Inhibition

Fragile X syndrome (FXS) is the leading monogenic cause of autism and intellectual disability. FXS is caused by loss of expression of fragile X mental retardation protein (FMRP), an RNA-binding protein that regulates translation of numerous mRNA targets, some of which are present at synapses. While protein synthesis deficits have long been postulated as an etiology of FXS, how FMRP loss affects distributions of newly synthesized proteins is unknown. Here we investigated the role of FMRP in regulating expression of new copies of the synaptic protein PSD95 in an in vitro model of synaptic plasticity. We find that local BDNF application promotes persistent accumulation of new PSD95 at stimulated synapses and dendrites of cultured neurons, and that this accumulation is absent in FMRP-deficient mouse neurons. New PSD95 accumulation at sites of BDNF stimulation does not require known mechanisms regulating FMRP–mRNA interactions but instead requires the PI3K-mTORC1-S6K1 pathway. Surprisingly, in FMRP-deficient neurons, BDNF induction of new PSD95 accumulation can be restored by mTORC1-S6K1 blockade, suggesting that constitutively high mTORC1-S6K1 activity occludes PSD95 regulation by BDNF and that alternative pathways exist to mediate induction when mTORC1-S6K1 is inhibited. This study provides direct evidence for deficits in local protein synthesis and accumulation of newly synthesized protein in response to local stimulation in FXS, and supports mTORC1-S6K1 pathway inhibition as a potential therapeutic approach for FXS.

scholarly journals Fragile X Mental Retardation Protein FMRP Binds mRNAs in the Nucleus

2008 ◽  
Vol 29 (1) ◽  
pp. 214-228 ◽  
Author(s):  
Miri Kim ◽  
Michel Bellini ◽  
Stephanie Ceman
Keyword(s):  
Mental Retardation ◽  
Nuclear Export ◽  
Rna Binding ◽  
Fragile X ◽  
Simian Virus 40 ◽  
Nuclear Localization Sequence ◽  
Dependent Manner ◽  
Nuclear Export Sequence ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein

ABSTRACT The fragile X mental retardation protein FMRP is an RNA binding protein that associates with a large collection of mRNAs. Since FMRP was previously shown to be a nucleocytoplasmic shuttling protein, we examined the hypothesis that FMRP binds its cargo mRNAs in the nucleus. The enhanced green fluorescent protein-tagged FMRP construct (EGFP-FMRP) expressed in Cos-7 cells was efficiently exported from the nucleus in the absence of its nuclear export sequence and in the presence of a strong nuclear localization sequence (the simian virus 40 [SV40] NLS), suggesting an efficient mechanism for nuclear export. We hypothesized that nuclear FMRP exits the nucleus through its bound mRNAs. Using silencing RNAs to the bulk mRNA exporter Tap/NXF1, we observed a significantly increased number of cells containing EGFP-FMRP in the nucleus, which was further augmented by removal of FMRP's nuclear export sequence. Nuclear-retained SV40-FMRP could be released upon treatment with RNase. Further, Tap/NXF1 coimmunoprecipitated with EGFP-FMRP in an RNA-dependent manner and contained the FMR1 mRNA. To determine whether FMRP binds pre-mRNAs cotranscriptionally, we expressed hemagglutinin-SV40 FMRP in amphibian oocytes and found it, as well as endogenous Xenopus FMRP, on the active transcription units of lampbrush chromosomes. Collectively, our data provide the first lines of evidence that FMRP binds mRNA in the nucleus.

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