scholarly journals Translation regulation of mRNAs by the fragile X family of proteins through the microRNA pathway

RNA Biology ◽  
2009 ◽  
Vol 6 (2) ◽  
pp. 175-178 ◽  
Author(s):  
Anne Cheever ◽  
Stephanie Ceman
Keyword(s):  
Fragile X ◽  
Translation Regulation ◽  
Microrna Pathway

scholarly journals Role of microRNA Pathway in Mental Retardation

2007 ◽  
Vol 7 ◽  
pp. 146-154 ◽  
Author(s):  
Abrar Qurashi ◽  
Shuang Chang ◽  
Peng Jin
Keyword(s):  
Mental Retardation ◽  
Fragile X Syndrome ◽  
Genetic Basis ◽  
Fragile X ◽  
Biological Pathways ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein ◽  
Mirna Pathway ◽  
Microrna Pathway

Deficits in cognitive functions lead to mental retardation (MR). Understanding the genetic basis of inherited MR has provided insights into the pathogenesis of MR. Fragile X syndrome is one of the most common forms of inherited MR, caused by the loss of functional Fragile X Mental Retardation Protein (FMRP).MicroRNAs (miRNAs) are endogenous, single-stranded RNAs between 18 and 25 nucleotides in length, which have been implicated in diversified biological pathways. Recent studies have linked the miRNA pathway to fragile X syndrome. Here we review the role of the miRNA pathway in fragile X syndrome and discuss its implication in MR in general.

Role of microRNA pathway in Fragile X mental retardation

MicroRNAs ◽  
2009 ◽  
pp. 363-371
Author(s):  
Keith Szulwach ◽  
Peng Jin ◽  
Sidney Altman ◽  
Victor R. Ambros
Keyword(s):  
Mental Retardation ◽  
Fragile X ◽  
Fragile X Mental Retardation ◽  
Microrna Pathway

scholarly journals Function of FMRP domains in regulating distinct roles of neuronal protein synthesis

2021 ◽  
Author(s):  
Michelle Ninochka D'Souza ◽  
Sarayu Ramakrishna ◽  
Bindushree K Radhakrishna ◽  
Vishwaja Jhaveri ◽  
Sreenath Ravindran ◽  
...  
Keyword(s):  
Rna Binding ◽  
Fragile X ◽  
Translation Regulation ◽  
Synaptic Development ◽  
Neuronal Protein ◽  
C Terminus ◽  
Mental Retardation Protein ◽  
Dependent Transport ◽  
Fundamental Mechanism

The Fragile X Mental Retardation Protein (FMRP) is an RNA Binding Protein that regulates translation of mRNAs, essential for synaptic development and plasticity. FMRP interacts with a specific set of mRNAs and aids in their microtubule dependent transport and regulates their translation through its association with ribosomes. However, the biochemical role of individual domains of FMRP in forming neuronal granules and associating with microtubules and ribosomes is currently undefined. Here, we report that the C-terminus domain of FMRP is sufficient to bind to ribosomes as well as polysomes akin to the full-length protein. Furthermore, the C-terminus domain alone is essential and responsible for FMRP-mediated translation repression in neurons. However, FMRP-mediated puncta formation and microtubule association is favored by the synergistic combination of FMRP domains and not by individual domains. Interestingly, we show that the phosphorylation of hFMRP at Serine-500 is important in modulating the dynamics of translation by controlling ribosome/polysome association. This is a fundamental mechanism governing the size and number of FMRP puncta, which appear to contain actively translating ribosomes. Finally through the use of pathogenic mutations, we emphasize the hierarchy of the domains of FMRP in their contribution to translation regulation.

scholarly journals Cells Lacking the Fragile X Mental Retardation Protein (FMRP) have Normal RISC Activity but Exhibit Altered Stress Granule Assembly

2009 ◽  
Vol 20 (1) ◽  
pp. 428-437 ◽  
Author(s):  
Marie-Cécile Didiot ◽  
Murugan Subramanian ◽  
Eric Flatter ◽  
Jean-Louis Mandel ◽  
Hervé Moine
Keyword(s):  
Mental Retardation ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Fragile X ◽  
Stress Granule ◽  
Translation Regulation ◽  
Positive Role ◽  
Granule Formation ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein

The fragile X mental retardation protein (FMRP) is an RNA-binding protein involved in the mRNA metabolism. The absence of FMRP in neurons leads to alterations of the synaptic plasticity, probably as a result of translation regulation defects. The exact molecular mechanisms by which FMRP plays a role in translation regulation have remained elusive. The finding of an interaction between FMRP and the RNA interference silencing complex (RISC), a master of translation regulation, has suggested that both regulators could be functionally linked. We investigated here this link, and we show that FMRP exhibits little overlap both physically and functionally with the RISC machinery, excluding a direct impact of FMRP on RISC function. Our data indicate that FMRP and RISC are associated to distinct pools of mRNAs. FMRP, unlike RISC machinery, associates with the pool of mRNAs that eventually goes into stress granules upon cellular stress. Furthermore, we show that FMRP plays a positive role in this process as the lack of FMRP or a point mutant causing a severe fragile X alter stress granule formation. Our data support the proposal that FMRP plays a role in controlling the fate of mRNAs after translation arrest.

Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway

2004 ◽  
Vol 7 (2) ◽  
pp. 113-117 ◽  
Author(s):  
Peng Jin ◽  
Daniela C Zarnescu ◽  
Stephanie Ceman ◽  
Mika Nakamoto ◽  
Julie Mowrey ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Genetic Interaction ◽  
Fragile X ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein ◽  
Microrna Pathway

scholarly journals FMRP and MOV10 regulate Dicer1 expression and dendrite development

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260005
Author(s):  
Monica C. Lannom ◽  
Joshua Nielsen ◽  
Aatiqa Nawaz ◽  
Temirlan Shilikbay ◽  
Stephanie Ceman
Keyword(s):  
Fragile X ◽  
Leukemia Virus ◽  
Dendritic Morphology ◽  
Neuronal Morphology ◽  
Translation Regulation ◽  
Neuro2a Cell ◽  
Dendrite Development ◽  
Moloney Leukemia Virus ◽  
Dicer Expression ◽  
Dicer1 Expression

Fragile X syndrome results from the loss of expression of the Fragile X Mental Retardation Protein (FMRP). FMRP and RNA helicase Moloney Leukemia virus 10 (MOV10) are important Argonaute (AGO) cofactors for miRNA-mediated translation regulation. We previously showed that MOV10 functionally associates with FMRP. Here we quantify the effect of reduced MOV10 and FMRP expression on dendritic morphology. Murine neurons with reduced MOV10 and FMRP phenocopied Dicer1 KO neurons which exhibit impaired dendritic maturation Hong J (2013), leading us to hypothesize that MOV10 and FMRP regulate DICER expression. In cells and tissues expressing reduced MOV10 or no FMRP, DICER expression was significantly reduced. Moreover, the Dicer1 mRNA is a Cross-Linking Immunoprecipitation (CLIP) target of FMRP Darnell JC (2011), MOV10 Skariah G (2017) and AGO2 Kenny PJ (2020). MOV10 and FMRP modulate expression of DICER1 mRNA through its 3’untranslated region (UTR) and introduction of a DICER1 transgene restores normal neurite outgrowth in the Mov10 KO neuroblastoma Neuro2A cell line and branching in MOV10 heterozygote neurons. Moreover, we observe a global reduction in AGO2-associated microRNAs isolated from Fmr1 KO brain. We conclude that the MOV10-FMRP-AGO2 complex regulates DICER expression, revealing a novel mechanism for regulation of miRNA production required for normal neuronal morphology.

scholarly journals Investigation of mRNA Translation Regulation by FMRP via the Microrna Pathway

2018 ◽  
Vol 114 (3) ◽  
pp. 442a-443a
Author(s):  
Joshua A. Imperatore ◽  
Brett A. DeMarco ◽  
Mihaela Rita Mihailescu
Keyword(s):  
Mrna Translation ◽  
Translation Regulation ◽  
Microrna Pathway
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