scholarly journals The RNA binding protein fragile X mental retardation protein promotes myelin sheath growth

Glia ◽  
2019 ◽  
Vol 68 (3) ◽  
pp. 495-508 ◽  
Author(s):  
Caleb A. Doll ◽  
Katie M. Yergert ◽  
Bruce H. Appel
Keyword(s):  
Mental Retardation ◽  
Myelin Sheath ◽  
Rna Binding ◽  
Fragile X ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein

A novel role of fragile X mental retardation protein in pre-mRNA alternative splicing through RNA-binding protein 14

Neuroscience ◽  
2017 ◽  
Vol 349 ◽  
pp. 64-75 ◽  
Author(s):  
Lin-Tao Zhou ◽  
Shun-Hua Ye ◽  
Hai-Xuan Yang ◽  
Yong-Ting Zhou ◽  
Qi-Hua Zhao ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Alternative Splicing ◽  
Rna Binding ◽  
Fragile X ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein

scholarly journals The nuclear MicroSpherule protein 58 is a novel RNA-binding protein that interacts with fragile X mental retardation protein in polyribosomal mRNPs from neurons

2006 ◽  
Vol 15 (9) ◽  
pp. 1525-1538 ◽  
Author(s):  
Laetitia Davidovic ◽  
Elias Bechara ◽  
Maud Gravel ◽  
Xavier H. Jaglin ◽  
Sandra Tremblay ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Rna Binding ◽  
Fragile X ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein

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 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.

scholarly journals Temporal-specific roles of fragile X mental retardation protein in the development of the hindbrain auditory circuit

Development ◽  
2020 ◽  
Vol 147 (21) ◽  
pp. dev188797
Author(s):  
Xiaoyu Wang ◽  
Ayelet Kohl ◽  
Xiaoyan Yu ◽  
Diego A. R. Zorio ◽  
Avihu Klar ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Rna Binding ◽  
Fragile X ◽  
Neuronal Cell ◽  
High Specificity ◽  
Fragile X Mental Retardation ◽  
Midline Crossing ◽  
Mental Retardation Protein ◽  
Axonal Targeting

ABSTRACTFragile X mental retardation protein (FMRP) is an RNA-binding protein abundant in the nervous system. Functional loss of FMRP leads to sensory dysfunction and severe intellectual disabilities. In the auditory system, FMRP deficiency alters neuronal function and synaptic connectivity and results in perturbed processing of sound information. Nevertheless, roles of FMRP in embryonic development of the auditory hindbrain have not been identified. Here, we developed high-specificity approaches to genetically track and manipulate throughout development of the Atoh1+ neuronal cell type, which is highly conserved in vertebrates, in the cochlear nucleus of chicken embryos. We identified distinct FMRP-containing granules in the growing axons of Atoh1+ neurons and post-migrating NM cells. FMRP downregulation induced by CRISPR/Cas9 and shRNA techniques resulted in perturbed axonal pathfinding, delay in midline crossing, excess branching of neurites, and axonal targeting errors during the period of circuit development. Together, these results provide the first in vivo identification of FMRP localization and actions in developing axons of auditory neurons, and demonstrate the importance of investigating early embryonic alterations toward understanding the pathogenesis of neurodevelopmental disorders.

scholarly journals Conformational-Dependent and Independent RNA Binding to the Fragile X Mental Retardation Protein

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Xin Yan ◽  
Robert B. Denman
Keyword(s):  
Mental Retardation ◽  
Rna Binding ◽  
Fragile X ◽  
In Vitro Transcription ◽  
Rna Transcripts ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein ◽  
Arginine Residues ◽  
Rnase Digestion

The interaction between the fragile X mental retardation protein (FMRP) and BC1 RNA has been the subject of controversy. We probed the parameters of RNA binding to FMRP in several ways. Nondenaturing agarose gel analysis showed that BC1 RNA transcripts produced by in vitro transcription contain a population of conformers, which can be modulated by preannealing. Accordingly, FMRP differentially binds to the annealed and unannealed conformer populations. Using partial RNase digestion, we demonstrate that annealed BC1 RNA contains a unique conformer that FMRP likely binds. We further demonstrate that this interaction is 100-fold weaker than that the binding of eEF-1A mRNA and FMRP, and that preannealing is not a general requirement for FMRP's interaction with RNA. In addition, binding does not require the N-terminal 204 amino acids of FMRP, methylated arginine residues and can be recapitulated by both fragile X paralogs. Altogether, our data continue to support a model in which BC1 RNA functions independently of FMRP.

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