Silencing of the fragile X messenger ribonucleoprotein 1 () gene and a consequent lack of FMR protein (FMRP) synthesis are associated with fragile X syndrome, one of the most common inherited intellectual disabilities. FMRP is a multifunctional protein that is involved in many cellular functions in almost all subcellular compartments under both normal and cellular stress conditions in neuronal and non-neuronal cell types. This is achieved through its trafficking signals, nuclear localization signal (NLS), nuclear export signal (NES), and nucleolar localization signal (NoLS), as well as its RNA and protein binding domains, and it is modulated by various post-translational modifications such as phosphorylation, ubiquitination, sumoylation, and methylation. This review summarizes the recent advances in understanding the interaction networks of FMRP with a special focus on FMRP stress-related functions, including stress granule formation, mitochondrion and endoplasmic reticulum plasticity, ribosome biogenesis, cell cycle control, and DNA damage response.
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http://dx.doi.org/10.3390/biom14040399 | DOI Listing |
Int J Mol Sci
December 2024
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
(Fragile X messenger ribonucleoprotein 1), located on the X-chromosome, encodes the multi-functional FMR1 protein (FMRP), critical to brain development and function. Trinucleotide CGG repeat expansions at this locus cause a range of neurological disorders, collectively referred to as Fragile X-related conditions. The most well-known of these is Fragile X syndrome, a neurodevelopmental disorder associated with syndromic facial features, autism, intellectual disabilities, and seizures.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, CA 95817, USA.
Fragile X syndrome (FXS) is a genetic condition caused by the inheritance of alleles with >200 CGG repeats in the 5' UTR of the fragile X messenger ribonucleoprotein 1 () gene. These full mutation (FM) alleles are associated with DNA methylation and gene silencing, which result in intellectual disabilities, developmental delays, and social and behavioral issues. Mosaicism for both the size of the CGG repeat tract and the extent of its methylation is commonly observed in individuals with the FM.
View Article and Find Full Text PDFCells
December 2024
Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306, USA.
Fragile X Syndrome (FXS) presents with a constellation of phenotypes, including trouble regulating emotion and aggressive behaviors, disordered sleep, intellectual impairments, and atypical physical development. Genetic study of the X chromosome revealed that substantial repeat expansion of the 5' end of the gene fragile X messenger ribonucleoprotein 1 () promoted DNA methylation and, consequently, silenced expression of . Further analysis proved that shorter repeat expansions in also manifested in disease at later stages in life.
View Article and Find Full Text PDFeNeuro
January 2025
Department of Neuroscience, University of Wisconsin-Madison, Madison, WI, 53705
Fragile X autosomal homolog 1 (FXR1), a member of the fragile X messenger riboprotein 1 family, has been linked to psychiatric disorders including autism and schizophrenia. Parvalbumin (PV) interneurons play critical roles in cortical processing, and have been implicated in FXR1-linked mental illnesses. Targeted deletion of FXR1 from PV interneurons in mice has been shown to alter cortical excitability and elicit schizophrenia-like behavior.
View Article and Find Full Text PDFJBRA Assist Reprod
December 2024
Genetics Unit, Department of Pathology, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal.
Objective: There is a rising demand for assisted reproductive medicine, including sperm, oocyte and embryo donation. Besides medical and legal considerations, genetic testing, including carrier screening for multiple autosomal and X-linked recessive disorders plays an essential role in evaluating hereditary risk among donors and therefore exclude them from the donation process.
Methods: A retrospective study was conducted on oocyte donors from a private clinic of assisted reproduction who underwent genetic testing between June 2014 and September 2023.
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