Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG–repeat

Ashley, Claude T.; Sutcliffe, James S.; Kunst, Catherine B.; Leiner, Harold A.; Eichler, Evan E.; Nelson, David L.; Warren, Stephen T.

doi:10.1038/ng0793-244

Cited by 233 publications

(193 citation statements)

References 28 publications

Supporting

Mentioning

183

Contrasting

Unclassified

Order By: Relevance

“…As a result of the alternative splicing of the Fmr1 mRNA numerous isoforms of the protein can be synthesized, an argument in favor of particular cellular roles for the individual isoforms (Ashley et al 1993, Sittler et al 1996, Denman & Sung 2002. In addition, phosphorylation and methylation have been described as post-translational modification of FMRP , Stetler et al 2006.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

View full text Add to dashboard Cite

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 of FMR1 premutation 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 of Fmr1 mRNA 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 in Fmr1 expression, both at the protein and mRNA levels, were observed. FMRP levels increased upon follicular development while preantral and early antral follicles presented similar levels of Fmr1 transcripts with decreased expression in preovulatory follicles. These observations suggest that Fmr1 expression 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 of Fmr1, both at mRNA and protein levels, during rat follicular development.

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Mice share a high level of nucleotide and amino acid homology with humans (Verkerk et al, 1991;Ashley et al, 1993). In addition, the tissue specificity and temporal and spatial expression profile of FMRP are similar in both species, thus making the mouse a suitable model for the study of this disorder (Hinds et al, 1993;Bakker et al, 2000).…”

Section: The Mouse Model and Molecular Mechanisms Of Fragile X Syndromementioning

confidence: 99%

Early developmental alterations in GABAergic protein expression in fragile X knockout mice

et al. 2010

View full text Add to dashboard Cite

The purpose of this study was to examine the expression of GABAergic proteins in Fmr1 knockout mice during brain maturation and to assess behavioural changes potentially linked to perturbations in the GABAergic system. Quantitative western blotting of the forebrain revealed that compared to wild-type mice, the GABA A receptor α1, β2, and δ subunits, and the GABA catabolic enzymes GABA transaminase and SSADH were down-regulated during postnatal development, while GAD65 was up-regulated in the adult knockout mouse forebrain. In tests of locomotor activity, the suppressive effect on motor activity of the GABA A β2/3 subunit-selective drug loreclezole was impaired in the mutant mice. In addition, sleep time induced by the GABA A β2/3-selective anaesthetic drug etomidate was decreased in the knockout mice. Our results indicate that disruptions in the GABAergic system in the developing brain may result in behavioural consequences in adults with fragile X syndrome.iii

show abstract

“…The presence of alternative splicing of FMR-I mRNA [90,91] suggests that there could be several forms of the FMR-I protein with various cellular functions. The cellular localization of the FMR-I gene product will be known very soon and clues about its function(s) should become available.…”

Section: Fmr-i Gene Function Knownmentioning

confidence: 99%

The fragile X syndrome: implications of molecular genetics for the clinical syndrome

Rousseau

1994

Eur J Clin Investigation

View full text Add to dashboard Cite

Abstract. The fragile X syndrome of mental retardation is one of the most common genetic diseases. Characterization of the mutations involved has greatly improved our knowledge of the transmission of fragile X syndrome and new DNA-based diagnostics tools significantly outperform cytogenetic testing both for establishing the diagnosis and for determining carrier status. Fragile X mutations consist of an expansion of a CGG trinucleotide repeat localized in a gene (FMR-1) that is abnormally methylated in all affected individuals. They are classified as premutations (asymptomatic) and full mutations (associated with the disease). Several different DNA analysis protocols are used for fragile X genotyping but only a few have been tested on large samples of individuals. There are several clinical indications for direct DNA genotyping for fragile X including mental retardation, learning disability or hyperactivity in children with or without a family history of mental retardation, the establishment of carrier diagnosis in fragile X families and prenatal screening of children from carrier women.

show abstract

Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG–repeat

Cited by 233 publications

References 28 publications

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

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

Early developmental alterations in GABAergic protein expression in fragile X knockout mice

The fragile X syndrome: implications of molecular genetics for the clinical syndrome

Contact Info

Product

Resources

About