ArticlePLoS genetics2013
A novel role for the RNA-binding protein FXR1P in myoblasts cell-cycle progression by modulating p21/Cdkn1a/Cip1/Waf1 mRNA stability.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 72 citations in OpenAlex.
- Contribution of FXR1 genetic polymorphisms to breast cancer susceptibility in Chinese females.Molecular genetics and genomics : MGG · 2026Article
- OTUD6B-mediated K48 deubiquitination of FXR1 forms a positive feedback loop activating MEK2/ERK signaling in colorectal cancer liver metastasis.Cell death & disease · 2026Article
- Muscle-specific isoforms of FXR1 are necessary for miR-1-mediated repression of connexin 43 and are downregulated in pediatric dilated cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2025Article
- The Spatial-Temporal Alternative Splicing Profile Reveals the Functional Diversity of FXR1 Isoforms in Myogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- An in-depth review of the function of RNA-binding protein FXR1 in neurodevelopment.Cell and tissue research · 2024Review
- PRMT5-mediated arginine methylation of FXR1 is essential for RNA binding in cancer cells.Nucleic acids research · 2024Article
- Molecular Regulation of Porcine Skeletal Muscle Development: Insights from Research on CDC23 Expression and Function.International journal of molecular sciences · 2024Article
- The multifaceted role of Fragile X-Related Protein 1 (FXR1) in cellular processes: an updated review on cancer and clinical applications.Cell death & disease · 2024Review
- Multi-Omic Analysis of CIC's Functional Networks Reveals Novel Interaction Partners and a Potential Role in Mitotic Fidelity.Cancers · 2023Article
- Genetic Deletion of FXR1 Reduces Intimal Hyperplasia and Induces Senescence in Vascular Smooth Muscle Cells.The American journal of pathology · 2023Article
- Diverse roles of biomolecular condensation in eukaryotic translational regulation.RNA biology · 2023Review
- Amyloid Properties of the FXR1 Protein Are Conserved in Evolution of Vertebrates.International journal of molecular sciences · 2022Article
- The Fragile X Protein Disordered Regions Bind a Novel RNA Target.Biochemistry · 2022Article
- The Fragile X Proteins Differentially Regulate Translation of Reporter mRNAs with G-quadruplex Structures.Journal of molecular biology · 2022Article
- Colorectal Cancer Chemotherapy Drug Bevacizumab May Induce Muscle Atrophy Through CDKN1A and TIMP4.Frontiers in oncology · 2022Article
- FXR1 regulation of parvalbumin interneurons in the prefrontal cortex is critical for schizophrenia-like behaviors.Molecular psychiatry · 2021Article
- Expression of Endogenous Angiotensin-Converting Enzyme 2 in Human Induced Pluripotent Stem Cell-Derived Retinal Organoids.International journal of molecular sciences · 2021Article
- MBNL2 Regulates DNA Damage Response via Stabilizing p21.International journal of molecular sciences · 2021Article
- Molecular and Immunohistochemical Expression of LTA4H and FXR1 in Canine Oral Melanoma.Frontiers in veterinary science · 2021Article
- RNA-Binding Proteins in the Post-transcriptional Control of Skeletal Muscle Development, Regeneration and Disease.Frontiers in cell and developmental biology · 2021Review
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Fragile X-Related 1 gene (FXR1) is a paralog of the Fragile X Mental Retardation 1 gene (FMR1), whose absence causes the Fragile X syndrome, the most common form of inherited intellectual disability. FXR1P plays an important role in normal muscle development, and its absence causes muscular abnormalities in mice, frog, and zebrafish. Seven alternatively spliced FXR1 transcripts have been identified and two of them are skeletal muscle-specific. A reduction of these isoforms is found in myoblasts from Facio-Scapulo Humeral Dystrophy (FSHD) patients. FXR1P is an RNA-binding protein involved in translational control; however, so far, no mRNA target of FXR1P has been linked to the drastic muscular phenotypes caused by its absence. In this study, gene expression profiling of C2C12 myoblasts reveals that transcripts involved in cell cycle and muscular development pathways are modulated by Fxr1-depletion. We observed an increase of p21--a regulator of cell-cycle progression--in Fxr1-knocked-down mouse C2C12 and FSHD human myoblasts. Rescue of this molecular phenotype is possible by re-expressing human FXR1P in Fxr1-depleted C2C12 cells. FXR1P muscle-specific isoforms bind p21 mRNA via direct interaction with a conserved G-quadruplex located in its 3' untranslated region. The FXR1P/G-quadruplex complex reduces the half-life of p21 mRNA. In the absence of FXR1P, the upregulation of p21 mRNA determines the elevated level of its protein product that affects cell-cycle progression inducing a premature cell-cycle exit and generating a pool of cells blocked at G0. Our study describes a novel role of FXR1P that has crucial implications for the understanding of its role during myogenesis and muscle development, since we show here that in its absence a reduced number of myoblasts will be available for muscle formation/regeneration, shedding new light into the pathophysiology of FSHD.
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