FMR1

Last updated
FMR1
Protein FMR1 PDB 2bkd.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases FMR1 , FMRP, FRAXA, POF, POF1, fragile X mental retardation 1, FMRP translational regulator 1, fragile X messenger ribonucleoprotein 1
External IDs OMIM: 309550 MGI: 95564 HomoloGene: 1531 GeneCards: FMR1
Orthologs
SpeciesHumanMouse
Entrez

2332

14265

Ensembl

ENSG00000102081

ENSMUSG00000000838

UniProt

Q06787

P35922

RefSeq (mRNA)

NM_001185075
NM_001185076
NM_001185081
NM_001185082
NM_002024

NM_001290424
NM_008031
NM_001374719

RefSeq (protein)

NP_001172004
NP_001172005
NP_001172010
NP_001172011
NP_002015

n/a

Location (UCSC) Chr X: 147.91 – 147.95 Mb Chr X: 67.72 – 67.76 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
Location of FMR1 on the X chromosome. Fmr1.jpeg
Location of FMR1 on the X chromosome.

FMR1 (Fragile X Messenger Ribonucleoprotein 1) is a human gene [5] that codes for a protein called fragile X messenger ribonucleoprotein, or FMRP. [6] This protein, most commonly found in the brain, is essential for normal cognitive development and female reproductive function. Mutations of this gene can lead to fragile X syndrome, intellectual disability, premature ovarian failure, autism, Parkinson's disease, developmental delays and other cognitive deficits. [7] The FMR1 premutation is associated with a wide spectrum of clinical phenotypes that affect more than two million people worldwide. [8]

Function

Synaptic plasticity

FMRP has a diverse array of functions throughout different areas of the neuron; however these functions have not been fully characterized. FMRP has been suggested to play roles in nucleocytoplasmic shuttling of mRNA, dendritic mRNA localization, and synaptic protein synthesis. [9] Studies of Fragile X syndrome have significantly aided in the understanding of the functionality of FMRP through the observed effects of FMRP loss on neurons. A mouse model of Fragile X Messenger Ribonucleoprotein implicated the involvement of FMRP in synaptic plasticity. [10] Synaptic plasticity requires the production of new proteins in response to activation of synaptic receptors. It is the production of proteins in response to stimulation which is hypothesized to allow for the permanent physical changes and altered synaptic connections that are linked with the processes of learning and memory.

Group 1 metabotropic glutamate receptor (mGluR) signaling has been implicated in playing an important role in FMRP-dependent synaptic plasticity. Post-synaptic mGluR stimulation results in the up-regulation of protein synthesis through a second messenger system. [11] A role for mGluR in synaptic plasticity is further evidenced by the observation of dendritic spine elongation following mGluR stimulation. [12] Furthermore, mGluR activation results in the synthesis of FMRP near synapses. The produced FMRP associates with polyribosomal complexes after mGluR stimulation, proposing the involvement of Fragile X Messenger Ribonucleoprotein in the process of translation. This further advocates a role for FMRP in synaptic protein synthesis and the growth of synaptic connections. [13] The loss of FMRP results in an abnormal dendritic spine phenotype. Specifically, deletion of the FMR1 gene in a sample of mice resulted in an increase in spine synapse number. [14]

Role in translation

The proposed mechanism of FMRP's effect upon synaptic plasticity are through its role as a negative regulator of translation. FMRP is an RNA-binding protein which associates with polyribosomes. [13] [15] The RNA-binding abilities of FMRP are dependent upon its KH domains and RGG boxes. The KH domain is a conserved motif which characterizes many RNA-binding proteins. Mutagenesis of this domain resulted in impaired FMRP binding to RNA. [16]

FMRP has been shown to inhibit translation of mRNA. Mutation of the FMRP protein resulted in the inability to repress translation as opposed to the wild-type counterpart which was able to do so. [17] As previously mentioned, mGluR stimulation is associated with increased FMRP protein levels. In addition, mGluR stimulation results in increased levels of FMRP target mRNAs. A study found basal levels of proteins encoded by these target mRNAs to be significantly elevated and improperly regulated in FMRP deficient mice. [18]

FMRP translation repression acts by inhibiting the initiation of translation. FMRP directly binds CYFIP1, which in turn binds the translation initiation factor eIF4E. The FMRP-CYFIP1 complex prohibits eIF4E-dependent initiation, thereby acting to repress translation. [19] When applied to the observed phenotype in fragile X Syndrome, the excess protein levels and reduction of translational control can be explained by the loss of translational repression by FMRP in fragile X syndrome. [19] [20] FMRP acts to control translation of a large group of target mRNAs; however the extent of FMRPs translational control is unknown. The protein has been shown to repress the translation of target mRNAs at synapses, including those encoding the cytoskeletal proteins Arc/Arg3.1 and MAP1B, and the CaM kinase II. [21] In addition, FMRP binds PSD-95 and GluR1/2 mRNAs. Importantly, these FMRP-binding mRNAs play significant roles in neuronal plasticity.

FMRP translational control has been shown to be regulated by mGluR signaling. mGluR stimulation may result in the transportation of mRNA complexes to synapses for local protein synthesis. FMRP granules have been shown to localize with MAP1B mRNA and ribosomal RNA in dendrites, suggesting this complex as a whole may need to be transported to dendrites for local protein synthesis. In addition, microtubules were found to be a necessary component for the mGluR-dependent translocation of FMRP into dendrites. [9] FMRP may play an additional role in local protein synthesis by aiding in the association of mRNA cargo and microtubules. [22] Thus, FMRP is able to regulate transport efficacy, as well as repression of translation during transport. Finally, FMRP synthesis, ubiquitination, and proteolysis occur rapidly in response to mGluR signaling, suggesting an extremely dynamic role of the translational regulator. [18]

Gene expression

The FMR1 gene is located on the X chromosome and contains a repeated CGG trinucleotide. In most people, the CGG segment is repeated approximately 5-44 times. Higher numbers of repeats of the CGG segment are associated with impaired cognitive and reproductive function. If a person has 45-54 repeats this is considered the "gray zone" or borderline risk, 55-200 repeats is called premutation, and more than 200 repeats is considered a full mutation of the FMR1 gene according to the American College of Medical Genetics and Genomics. [23] The first complete DNA sequence of the repeat expansion in someone with the full mutation was generated by scientists in 2012 using SMRT sequencing. [24] This is an example of a Trinucleotide repeat disorder. Trinucleotide repeat expansion is likely a consequence of strand slippage either during DNA repair or DNA replication. [25]

FMRP is a chromatin-binding protein that functions in the DNA damage response. [26] [27] FMRP occupies sites on meiotic chromosomes and regulates the dynamics of the DNA damage response machinery during spermatogenesis. [26]

The FMR1 gene can be found on the long (q) arm of the X chromosome at position 27.3, from base pair 146,699,054 to base pair 146,738,156

Fragile X syndrome

Almost all cases of fragile X syndrome are caused by expansion of the CGG trinucleotide repeat in the FMR1 gene. In these cases, CGG is abnormally repeated from 200 to more than 1,000 times. As a result, this part of the FMR1 gene is methylated, which silences the gene (it is turned off and does not make any protein). Without adequate FMR1, severe learning disabilities or intellectual disabilities can develop, along with physical abnormalities seen in fragile X syndrome.

Fewer than 1% of all cases of fragile X syndrome are caused by mutations that delete part or all of the FMR1 gene, or change a base pair, leading to a change in one of the amino acids in the gene. These mutations disrupt the 3-dimensional shape of FMRP or prevent the protein from being synthesized, leading to the signs and symptoms of fragile X syndrome.

A CGG sequence in the FMR1 gene that is repeated between 55 and 200 times is described as a premutation. Although most individuals with the premutation are intellectually normal, some of these individuals have mild versions of the physical features seen in fragile X syndrome (such as prominent ears) and may experience mental health problems such as anxiety or depression.

Fragile X-associated tremor/ataxia syndrome

Premutations are associated with an increased risk of fragile X-associated tremor/ataxia syndrome (FXTAS). FXTAS is characterized by ataxia (loss of coordination), tremor, memory loss, loss of sensation in the lower extremities (peripheral neuropathy) and mental and behavioral changes. The disorder usually develops late in life.

Premature ovarian aging

The FMR1 gene plays a very important role in ovarian function, independent from cognitive/neurological effects. Minor expansions of CGG repeats that do not cause fragile X syndrome are associated with an increased risk for premature ovarian aging, also called occult primary ovarian insufficiency, a condition in which women prematurely deplete their ovarian function. [28] [29] [30]

Polycystic ovarian syndrome

A very specific sub-genotype of FMR1 has been found to be associated with polycystic ovarian syndrome (PCOS). The gene expression, called heterozygous-normal/low may cause PCOS-like excessive follicle activity and hyperactive ovarian function when women are younger.

Interactions

FMR1 has been shown to interact with:

Related Research Articles

<span class="mw-page-title-main">Fragile X syndrome</span> X-linked dominant genetic disorder

Fragile X syndrome (FXS) is a genetic disorder characterized by mild-to-moderate intellectual disability. The average IQ in males with FXS is under 55, while about two thirds of affected females are intellectually disabled. Physical features may include a long and narrow face, large ears, flexible fingers, and large testicles. About a third of those affected have features of autism such as problems with social interactions and delayed speech. Hyperactivity is common, and seizures occur in about 10%. Males are usually more affected than females.

Macroorchidism is a disorder found in males, specifically in children, where a subject has abnormally large testes. The condition is commonly inherited in connection with fragile X syndrome (FXS), which is also the second most common genetic cause of intellectual disability. The condition is also a rare sign of the McCune-Albright syndrome. The opposite of macroorchidism is called microorchidism, which is the condition of abnormally small testes.

RNA-binding proteins are proteins that bind to the double or single stranded RNA in cells and participate in forming ribonucleoprotein complexes. RBPs contain various structural motifs, such as RNA recognition motif (RRM), dsRNA binding domain, zinc finger and others. They are cytoplasmic and nuclear proteins. However, since most mature RNA is exported from the nucleus relatively quickly, most RBPs in the nucleus exist as complexes of protein and pre-mRNA called heterogeneous ribonucleoprotein particles (hnRNPs). RBPs have crucial roles in various cellular processes such as: cellular function, transport and localization. They especially play a major role in post-transcriptional control of RNAs, such as: splicing, polyadenylation, mRNA stabilization, mRNA localization and translation. Eukaryotic cells express diverse RBPs with unique RNA-binding activity and protein–protein interaction. According to the Eukaryotic RBP Database (EuRBPDB), there are 2961 genes encoding RBPs in humans. During evolution, the diversity of RBPs greatly increased with the increase in the number of introns. Diversity enabled eukaryotic cells to utilize RNA exons in various arrangements, giving rise to a unique RNP (ribonucleoprotein) for each RNA. Although RBPs have a crucial role in post-transcriptional regulation in gene expression, relatively few RBPs have been studied systematically.It has now become clear that RNA–RBP interactions play important roles in many biological processes among organisms.

A trinucleotide repeat expansion, also known as a triplet repeat expansion, is the DNA mutation responsible for causing any type of disorder categorized as a trinucleotide repeat disorder. These are labelled in dynamical genetics as dynamic mutations. Triplet expansion is caused by slippage during DNA replication, also known as "copy choice" DNA replication. Due to the repetitive nature of the DNA sequence in these regions, 'loop out' structures may form during DNA replication while maintaining complementary base pairing between the parent strand and daughter strand being synthesized. If the loop out structure is formed from the sequence on the daughter strand this will result in an increase in the number of repeats. However, if the loop out structure is formed on the parent strand, a decrease in the number of repeats occurs. It appears that expansion of these repeats is more common than reduction. Generally, the larger the expansion the more likely they are to cause disease or increase the severity of disease. Other proposed mechanisms for expansion and reduction involve the interaction of RNA and DNA molecules.

<span class="mw-page-title-main">Neurexin</span> Protein family

Neurexins (NRXN) are a family of presynaptic cell adhesion proteins that have roles in connecting neurons at the synapse. They are located mostly on the presynaptic membrane and contain a single transmembrane domain. The extracellular domain interacts with proteins in the synaptic cleft, most notably neuroligin, while the intracellular cytoplasmic portion interacts with proteins associated with exocytosis. Neurexin and neuroligin "shake hands," resulting in the connection between the two neurons and the production of a synapse. Neurexins mediate signaling across the synapse, and influence the properties of neural networks by synapse specificity. Neurexins were discovered as receptors for α-latrotoxin, a vertebrate-specific toxin in black widow spider venom that binds to presynaptic receptors and induces massive neurotransmitter release. In humans, alterations in genes encoding neurexins are implicated in autism and other cognitive diseases, such as Tourette syndrome and schizophrenia.

<span class="mw-page-title-main">GRIK2</span> Protein-coding gene in the species Homo sapiens

Glutamate ionotropic receptor kainate type subunit 2, also known as ionotropic glutamate receptor 6 or GluR6, is a protein that in humans is encoded by the GRIK2 gene.

<span class="mw-page-title-main">FXR1</span> Protein-coding gene in the species Homo sapiens

Fragile X mental retardation syndrome-related protein 1 is a protein that in humans is encoded by the FXR1 gene.

<span class="mw-page-title-main">GRIK1</span> Protein-coding gene in the species Homo sapiens

Glutamate receptor, ionotropic, kainate 1, also known as GRIK1, is a protein that in humans is encoded by the GRIK1 gene.

<span class="mw-page-title-main">FXR2</span> Protein-coding gene in the species Homo sapiens

Fragile X mental retardation syndrome-related protein 2 is a protein that in humans is encoded by the FXR2 gene.

<span class="mw-page-title-main">AFF2</span> Protein-coding gene in humans

AF4/FMR2 family member 2 is a protein that in humans is encoded by the AFF2 gene. Mutations in AFF2 are implicated in cases of breast cancer.

<span class="mw-page-title-main">CGGBP1</span> Protein-coding gene in the species Homo sapiens

CGG triplet repeat-binding protein 1 is a protein that in humans is encoded by the CGGBP1 gene.

<span class="mw-page-title-main">NUFIP1</span> Protein-coding gene in the species Homo sapiens

Nuclear fragile X mental retardation-interacting protein 1 is a protein that in humans is encoded by the NUFIP1 gene.

Activity-dependent plasticity is a form of functional and structural neuroplasticity that arises from the use of cognitive functions and personal experience; hence, it is the biological basis for learning and the formation of new memories. Activity-dependent plasticity is a form of neuroplasticity that arises from intrinsic or endogenous activity, as opposed to forms of neuroplasticity that arise from extrinsic or exogenous factors, such as electrical brain stimulation- or drug-induced neuroplasticity. The brain's ability to remodel itself forms the basis of the brain's capacity to retain memories, improve motor function, and enhance comprehension and speech amongst other things. It is this trait to retain and form memories that is associated with neural plasticity and therefore many of the functions individuals perform on a daily basis. This plasticity occurs as a result of changes in gene expression which are triggered by signaling cascades that are activated by various signaling molecules during increased neuronal activity.

<span class="mw-page-title-main">Fragile X-associated tremor/ataxia syndrome</span>

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder most frequently seen in male premutation carriers of Fragile X syndrome (FXS) over the age of 50. The main clinical features of FXTAS include problems of movement with cerebellar gait ataxia and action tremor. Associated features include parkinsonism, cognitive decline, and dysfunction of the autonomic nervous system. FXTAS is found in Fragile X "premutation" carriers, which is defined as a trinucleotide repeat expansion of 55-200 CGG repeats in the Fragile X mental retardation-1 (FMR1) gene. 4-40 CGG repeats in this gene is considered normal, while individual with >200 repeats have full Fragile X Syndrome.

<span class="mw-page-title-main">Bantam microRNA</span>

In molecular biology, bantam microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

<span class="mw-page-title-main">FMR1-AS1 gene</span> Non-coding RNA in the species Homo sapiens

In molecular biology, FMR1 antisense RNA 1 (FMR1-AS1), also known as ASFMR1 or FMR4, is a long non-coding RNA. The FMR1-AS1 gene overlaps, and is antisense to, the CGG repeat region of the FMR1 gene. Its expression is upregulated in fragile X syndrome premutation carriers, and silenced in patients with fragile X syndrome. FMR1-AS1 has an anti-apoptotic function.

Fragile X-associated Primary Ovarian Insufficiency (FXPOI) is the most common genetic cause of premature ovarian failure in women with a normal karyotype 46, XX. The expansion of a CGG repeat in the 5' untranslated region of the FMR1 gene from the normal range of 5-45 repeats to the premutation range of 55-199 CGGs leads to risk of FXPOI for ovary-bearing individuals. About 1:150-1:200 women in the US population carry a premutation. Women who carry an FMR1 premutation have a roughly 20% risk of being diagnosed with FXPOI, compared to 1% for the general population, and an 8-15% risk of developing the neurogenerative tremor/ataxia disorder (FXTAS). FMR1 premutation women are also at increased risk of having a child with a CGG repeat that is expanded to >200 repeats. Individuals with a full mutation, unlike the premutation, produce little to no mRNA or protein from the FMR1 gene and are affected with Fragile X syndrome.

Nagwa Abdel Meguid is an Egyptian geneticist and 2002 winner of the L’Oreal UNESCO Award for Women in Science for Africa and the Middle East. Her research has "identified several genetic mutations that cause common syndromes such as the fragile X syndrome and Autism".

David L. Nelson is an American human geneticist, currently an associate director at the Intellectual and Developmental Disabilities Research Center (1995), and professor at the Department of Molecular and Human Genetics at Baylor College of Medicine BCM since 1999. Since 2018, he is the director at the Cancer and Cell Biology Ph.D program, and the director of Integrative Molecular and Biomedical Sciences Ph.D since 2015 at BCM.

Stephen T. Warren was an American geneticist and academic. He was the William Patterson Timmie Professor of Human Genetics and the Charles Howard Candler Chair of Human Genetics. He was the former Founding Chairman of the Department of Human Genetics at Emory University School of Medicine. He was an Investigator with the Howard Hughes Medical Institute from 1991 until 2002, when he resigned to found the Human Genetics department. Warren is well known for his work in the field of Human Genetics. His research was focused on the mechanistic understanding of fragile X syndrome, a leading cause of inherited developmental disability and autism. In 2020, Warren stepped down as department chair after 20 years in that position.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000102081 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000000838 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A, Reiner O, Richards S, Victoria MF, Zhang FP (May 1991). "Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome". Cell. 65 (5): 905–14. doi:10.1016/0092-8674(91)90397-H. PMID   1710175. S2CID   21463845.
  6. ↑ Verheij C, Bakker CE, de Graaff E, Keulemans J, Willemsen R, Verkerk AJ, Galjaard H, Reuser AJ, Hoogeveen AT, Oostra BA (June 1993). "Characterization and localization of the FMR-1 gene product associated with fragile X syndrome". Nature. 363 (6431): 722–4. Bibcode:1993Natur.363..722V. doi:10.1038/363722a0. hdl: 1765/56659 . PMID   8515814. S2CID   4331494.
  7. ↑ "Fragile X Messenger Ribonucleoprotein 1" The Human Gene Compendium
  8. ↑ Milà M, Rodriguez-Revenga L, Matilla-Dueñas A (October 2016). "FMR1 Premutation: Basic Mechanisms and Clinical Involvement". Cerebellum. 15 (5): 543–5. doi:10.1007/s12311-016-0808-7. PMID   27338822. S2CID   16002209.
  9. 1 2 Antar LN, Dictenberg JB, Plociniak M, Afroz R, Bassell GJ (August 2005). "Localization of FMRP-associated mRNA granules and requirement of microtubules for activity-dependent trafficking in hippocampal neurons". Genes, Brain and Behavior. 4 (6): 350–9. doi: 10.1111/j.1601-183X.2005.00128.x . PMID   16098134.
  10. ↑ Huber KM, Gallagher SM, Warren ST, Bear MF (May 2002). "Altered synaptic plasticity in a mouse model of fragile X mental retardation". Proceedings of the National Academy of Sciences of the United States of America. 99 (11): 7746–50. Bibcode:2002PNAS...99.7746H. doi: 10.1073/pnas.122205699 . PMC   124340 . PMID   12032354.
  11. ↑ Weiler IJ, Greenough WT (August 1993). "Metabotropic glutamate receptors trigger postsynaptic protein synthesis". Proceedings of the National Academy of Sciences of the United States of America. 90 (15): 7168–71. Bibcode:1993PNAS...90.7168W. doi: 10.1073/pnas.90.15.7168 . PMC   47097 . PMID   8102206.
  12. ↑ Vanderklish PW, Edelman GM (February 2002). "Dendritic spines elongate after stimulation of group 1 metabotropic glutamate receptors in cultured hippocampal neurons". Proceedings of the National Academy of Sciences of the United States of America. 99 (3): 1639–44. Bibcode:2002PNAS...99.1639V. doi: 10.1073/pnas.032681099 . PMC   122243 . PMID   11818568.
  13. 1 2 Weiler IJ, Irwin SA, Klintsova AY, Spencer CM, Brazelton AD, Miyashiro K, Comery TA, Patel B, Eberwine J, Greenough WT (May 1997). "Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation". Proceedings of the National Academy of Sciences of the United States of America. 94 (10): 5395–400. Bibcode:1997PNAS...94.5395W. doi: 10.1073/pnas.94.10.5395 . PMC   24689 . PMID   9144248.
  14. ↑ Antar LN, Li C, Zhang H, Carroll RC, Bassell GJ (2006). "Local functions for FMRP in axon growth cone motility and activity-dependent regulation of filopodia and spine synapses". Molecular and Cellular Neurosciences. 32 (1–2): 37–48. doi:10.1016/j.mcn.2006.02.001. PMID   16631377. S2CID   18257268.
  15. ↑ Brown V, Small K, Lakkis L, Feng Y, Gunter C, Wilkinson KD, Warren ST (June 1998). "Purified recombinant Fmrp exhibits selective RNA binding as an intrinsic property of the fragile X mental retardation protein". The Journal of Biological Chemistry. 273 (25): 15521–7. doi: 10.1074/jbc.273.25.15521 . PMID   9624140.
  16. ↑ Siomi H, Choi M, Siomi MC, Nussbaum RL, Dreyfuss G (April 1994). "Essential role for KH domains in RNA binding: impaired RNA binding by a mutation in the KH domain of FMR1 that causes fragile X syndrome". Cell. 77 (1): 33–9. doi:10.1016/0092-8674(94)90232-1. PMID   8156595. S2CID   35339859.
  17. ↑ Laggerbauer B, Ostareck D, Keidel EM, Ostareck-Lederer A, Fischer U (February 2001). "Evidence that fragile X mental retardation protein is a negative regulator of translation". Human Molecular Genetics. 10 (4): 329–38. doi: 10.1093/hmg/10.4.329 . PMID   11157796.
  18. 1 2 Hou L, Antion MD, Hu D, Spencer CM, Paylor R, Klann E (August 2006). "Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression". Neuron. 51 (4): 441–54. doi: 10.1016/j.neuron.2006.07.005 . PMID   16908410. S2CID   13915959.
  19. 1 2 Napoli I, Mercaldo V, Boyl PP, Eleuteri B, Zalfa F, De Rubeis S, Di Marino D, Mohr E, Massimi M, Falconi M, Witke W, Costa-Mattioli M, Sonenberg N, Achsel T, Bagni C (September 2008). "The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP". Cell. 134 (6): 1042–54. doi: 10.1016/j.cell.2008.07.031 . PMID   18805096. S2CID   14123165.
  20. ↑ Muddashetty RS, Kelić S, Gross C, Xu M, Bassell GJ (May 2007). "Dysregulated metabotropic glutamate receptor-dependent translation of AMPA receptor and postsynaptic density-95 mRNAs at synapses in a mouse model of fragile X syndrome". The Journal of Neuroscience. 27 (20): 5338–48. doi: 10.1523/JNEUROSCI.0937-07.2007 . PMC   6672337 . PMID   17507556.
  21. ↑ Zalfa F, Giorgi M, Primerano B, Moro A, Di Penta A, Reis S, Oostra B, Bagni C (February 2003). "The fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at synapses". Cell. 112 (3): 317–27. doi: 10.1016/S0092-8674(03)00079-5 . PMID   12581522. S2CID   14892764.
  22. ↑ Estes PS, O'Shea M, Clasen S, Zarnescu DC (October 2008). "Fragile X protein controls the efficacy of mRNA transport in Drosophila neurons". Molecular and Cellular Neurosciences. 39 (2): 170–9. doi:10.1016/j.mcn.2008.06.012. PMID   18655836. S2CID   24629325.
  23. ↑ "Technical Standards and Guidelines for Fragile X". American College of Medical Genetics. 2000-10-02. Retrieved 2013-03-29.
  24. ↑ Loomis EW, Eid JS, Peluso P, Yin J, Hickey L, Rank D, McCalmon S, Hagerman RJ, Tassone F, Hagerman PJ (January 2013). "Sequencing the unsequenceable: expanded CGG-repeat alleles of the fragile X gene". Genome Research. 23 (1): 121–8. doi:10.1101/gr.141705.112. PMC   3530672 . PMID   23064752.
  25. ↑ Usdin K, House NC, Freudenreich CH (2015). "Repeat instability during DNA repair: Insights from model systems". Crit. Rev. Biochem. Mol. Biol. 50 (2): 142–67. doi:10.3109/10409238.2014.999192. PMC   4454471 . PMID   25608779.
  26. 1 2 Alpatov R, Lesch BJ, Nakamoto-Kinoshita M, Blanco A, Chen S, Stützer A, Armache KJ, Simon MD, Xu C, Ali M, Murn J, Prisic S, Kutateladze TG, Vakoc CR, Min J, Kingston RE, Fischle W, Warren ST, Page DC, Shi Y (May 2014). "A chromatin-dependent role of the fragile X mental retardation protein FMRP in the DNA damage response". Cell. 157 (4): 869–81. doi:10.1016/j.cell.2014.03.040. PMC   4038154 . PMID   24813610.
  27. ↑ Dockendorff TC, Labrador M (May 2018). "The Fragile X Protein and Genome Function". Mol. Neurobiol. 56 (1): 711–721. doi:10.1007/s12035-018-1122-9. PMID   29796988. S2CID   44159474.
  28. ↑ Gleicher N, Barad DH (August 2010). "The FMR1 gene as regulator of ovarian recruitment and ovarian reserve". Obstetrical & Gynecological Survey. 65 (8): 523–30. doi:10.1097/OGX.0b013e3181f8bdda. PMID   20955631. S2CID   26409068.
  29. ↑ Chatterjee S, Maitra A, Kadam S, Patel Z, Gokral J, Meherji P (August 2009). "CGG repeat sizing in the FMR1 gene in Indian women with premature ovarian failure". Reproductive Biomedicine Online. 19 (2): 281–6. doi: 10.1016/s1472-6483(10)60086-7 . PMID   19712568.
  30. ↑ Streuli I, Fraisse T, Ibecheole V, Moix I, Morris MA, de Ziegler D (August 2009). "Intermediate and premutation FMR1 alleles in women with occult primary ovarian insufficiency". Fertility and Sterility. 92 (2): 464–70. doi: 10.1016/j.fertnstert.2008.07.007 . PMID   18973899.
  31. 1 2 Schenck A, Bardoni B, Moro A, Bagni C, Mandel JL (July 2001). "A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P". Proceedings of the National Academy of Sciences of the United States of America. 98 (15): 8844–9. Bibcode:2001PNAS...98.8844S. doi: 10.1073/pnas.151231598 . PMC   37523 . PMID   11438699.
  32. 1 2 3 Bardoni B, Castets M, Huot ME, Schenck A, Adinolfi S, Corbin F, Pastore A, Khandjian EW, Mandel JL (July 2003). "82-FIP, a novel FMRP (fragile X mental retardation protein) interacting protein, shows a cell cycle-dependent intracellular localization". Human Molecular Genetics. 12 (14): 1689–98. doi: 10.1093/hmg/ddg181 . PMID   12837692.
  33. 1 2 Siomi MC, Zhang Y, Siomi H, Dreyfuss G (July 1996). "Specific sequences in the fragile X syndrome protein FMR1 and the FXR proteins mediate their binding to 60S ribosomal subunits and the interactions among them". Molecular and Cellular Biology. 16 (7): 3825–32. doi:10.1128/mcb.16.7.3825. PMC   231379 . PMID   8668200.
  34. 1 2 Zhang Y, O'Connor JP, Siomi MC, Srinivasan S, Dutra A, Nussbaum RL, Dreyfuss G (November 1995). "The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2". The EMBO Journal. 14 (21): 5358–66. doi:10.1002/j.1460-2075.1995.tb00220.x. PMC   394645 . PMID   7489725.
  35. ↑ Ceman S, Brown V, Warren ST (December 1999). "Isolation of an FMRP-associated messenger ribonucleoprotein particle and identification of nucleolin and the fragile X-related proteins as components of the complex". Molecular and Cellular Biology. 19 (12): 7925–32. doi:10.1128/mcb.19.12.7925. PMC   84877 . PMID   10567518.
  36. ↑ Bardoni B, Schenck A, Mandel JL (December 1999). "A novel RNA-binding nuclear protein that interacts with the fragile X mental retardation (FMR1) protein". Human Molecular Genetics. 8 (13): 2557–66. doi: 10.1093/hmg/8.13.2557 . PMID   10556305.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.