<i>FMR1</i>
            Protein: Conserved RNP Family Domains and Selective RNA Binding

Ashley, Claude T.; Wilkinson, Keith D.; Reines, Daniel; Warren, Stephen T.

doi:10.1126/science.7692601

Cited by 669 publications

(476 citation statements)

References 27 publications

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“…As an RNA-binding protein, FMRP has been shown to bind to RNA HOMOPOLYMERS as well as a subset of brain transcripts in vitro [10]. FMRP is associated with actively translating polyribosomes in an RNA-dependent manner via messenger ribonucleoprotein (mRNP) particles [7].…”

Section: Glossarymentioning

confidence: 99%

“…This suggests that these two proteins might be involved in the transportation and/or translational control of a subset of mRNAs specifically regulated by FMRP [24]. Although FMRP has been shown to bind to 4% of brain mRNAs in vitro, the identity of the mRNA ligands specifically regulated by FMRP has remained elusive [10]. Several groups have taken different approaches to identify the mRNAs that are specifically bound by FMRP and the structure required for FMRP-RNA interaction [25 -27].…”

Section: Glossarymentioning

confidence: 99%

See 1 more Smart Citation

New insights into fragile X syndrome: from molecules to neurobehaviors

Jin

Warren

2003

Trends in Biochemical Sciences

189

124

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Fragile X syndrome -a common form of inherited mental retardation -is caused by the loss of the fragile X mental retardation 1 protein (FMRP). FMRP is an RNA-binding protein which forms a messenger ribonucleoprotein (mRNP) complex that associates with translating polyribosomes. It has been proposed that FMRP is involved in synaptic plasticity through the regulation of mRNA transportation and translation. Recent advances in the identification of the mRNA ligands that are bound by FMRP, the RNA sequence and structure required for FMRP -RNA interaction, and the physiological consequences of FMRP deficiency in the brain are important steps towards understanding the molecular pathogenesis of fragile X syndrome, and learning and memory in general.Fragile X syndrome is the most common form of inherited mental retardation, with the estimated prevalence of one in 4000 males and one in 8000 females. In addition to cognitive deficits, the phenotype of fragile X syndrome includes mildly abnormal facial features (a prominent jaw, high forehead and large ears), MACROORCHIDISM (see Glossary) in postpubescent males and subtle connective tissue abnormalities [1]. Many patients also manifest attention-deficit hyperactivity disorder and autistic-like behavior. As one of the first identified human disorders caused by trinucleotide repeat expansion, fragile X syndrome is the result of a massive CGG trinucleotide repeat expansion within the gene fragile X mental retardation 1 (FMR1). FMR1 is a highly conserved gene that consists of 17 exons, and spans , 38 kilobases (kb). Within the 4.4-kb FMR1 transcript, a CGG trinucleotide repeat is located in the 5 0 untranslated region (UTR) [2]. Among normal individuals, this CGG repeat is highly polymorphic in length and content, often punctuated by AGG interruptions. The normal repeat size ranges from 7 to , 54, with 30 repeats found in the most common allele. In most affected individuals, CGG repeats are massively expanded over 230 repeats (full mutation) and become abnormally hypermethylated, which results in the transcriptional silencing of FMR1 [1]. Identification of other mutations in FMR1 (e.g. deletions and a point mutation among patients with the typical phenotype, but without FRAGILE SITE expression) has confirmed that the FMR1 gene is the only gene involved in the pathogenesis of fragile X syndrome and the loss of FMR1 product -fragile X mental retardation protein (FMRP) -causes fragile X syndrome [1]. A mouse model of fragile X syndrome was created using gene targeting; the Fmr1-knockout mice exhibit macroorchidism and subtle deficits in learning and memory, which mimic the human phenotype [3].In this review, we discuss the recent progress in understanding the biological functions of FMRP and the physiological consequences of its absence that lead to mental retardation. Features of FMRPFMRP is widely expressed in fetal and adult tissues, with the most abundant expression in brain and testes [4]. FMRP, and its autosomal paralogs the fragile-X-related protein FXR1P and FXR2P, consist...

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Section: Glossarymentioning

confidence: 99%

Section: Glossarymentioning

confidence: 99%

New insights into fragile X syndrome: from molecules to neurobehaviors

Jin

Warren

2003

Trends in Biochemical Sciences

189

124

View full text Add to dashboard Cite

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“…Northern blot analysis of RNA from several human tissues indicated the presence of a 4.8kb FMR1 mRNA. The sequence predicts a full-length protein of 614. amino acids with an expected mass of 69 kDa (22). Antibodies against the human FMRP, fragile X mental retardation protein detected the presence of a similar protein expressed in mice in a wide variety of tissues, particularly in brain, testes, ovaries, thymus, oesophagus and spleen (23).…”

Section: Fragile X Mental Retardation Protein (Fmrp)mentioning

confidence: 99%

Chromosomal fragility and human genetic disorders

Baskaran

Brahmachari

2000

Indian J Clin Biochem

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The first report of X-linked mental retardation correlated with the presence of marker chromosome came in 1940. It was in 1990 that the molecular basis of fragile X syndrome was deciphered. This elucidation marked the discovery of a novel process of mutation designated as dynamic mutations, resulting in the expansion of a triplet repeat sequence within the human genome. Subsequently several human genetic disorders involving triplet repeat expansion have beer= discovered. Almost all the disorders are known to affect the nervous system and/or the brain. This review presents an overview of fragile sites in the genome and the molecular genetics of fragile X syndrome.

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“…Consequently, the gene is silenced and no mRNA is produced. The lack of the gene product, FMRP, an RNA-binding protein, is responsible for the mental retardation 5. Approximately 1/4000 males have fragile X syndrome and, by inference, about 1/8000 females have significant features of the syndrome (for review, see Crawford et al (2001)) 6.…”

Section: Introductionmentioning

confidence: 99%

Fragile X syndrome: Diagnostic and carrier testing

Sherman

Pletcher

Driscoll

2005

Genetics in Medicine

248

206

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The following are the recommendations of the American College of Medical Genetics (ACMG) Professional Practice and Guidelines Committee, convened to assist health care professionals in making decisions regarding genetic diagnosis and testing. The purpose of this document is to provide a brief overview of fragile X syndrome (FXS), and to make recommendations that can serve as general guidelines to aid clinicians in making referrals for diagnostic and carrier testing for this condition. Fragile X syndrome is the most common cause of inherited mental retardation and is caused by a mutation in the X-linked FMR1 gene. DNA studies are used for testing individuals with symptoms of FXS and individuals at risk for carrying the mutation. Genotypes are determined by examining the size of the trinucleotide repeat segment and the methylation status of the FMR1 gene. These guidelines supersede the 1994 ACMG statement of the same name.

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FMR1 Protein: Conserved RNP Family Domains and Selective RNA Binding

Cited by 669 publications

References 27 publications

New insights into fragile X syndrome: from molecules to neurobehaviors

New insights into fragile X syndrome: from molecules to neurobehaviors

Chromosomal fragility and human genetic disorders

Fragile X syndrome: Diagnostic and carrier testing

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