ArticlePloS one2012
The role of the 3'UTR region in the regulation of the ACVR1/Alk-2 gene expression.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Molecular, phenotypic aspects and therapeutic horizons of rare genetic bone disorders.BioMed research international · 2014Pooled it
- Fibroblasts in heterotopic ossification: mechanisms and therapeutic targets.International journal of biological sciences · 2025Review
- The role of miRNAs as biomarkers in heterotopic ossification.EFORT open reviews · 2024Review
- Pathophysiology and Emerging Molecular Therapeutic Targets in Heterotopic Ossification.International journal of molecular sciences · 2022Review
- Two Modulators of Skeletal Development: BMPs and Proteoglycans.Journal of developmental biology · 2022Review
- Competition between type I activin and BMP receptors for binding to ACVR2A regulates signaling to distinct Smad pathways.BMC biology · 2022Article
- Association analysis of polymorphisms rs12997 in ACVR1 and rs1043784 in BMP6 genes involved in bone morphogenic protein signaling pathway in primary angle-closure and pseudoexfoliation glaucoma patients of Saudi origin.BMC medical genetics · 2020Article
- Targeting heterotopic ossification by inhibiting activin receptor‑like kinase 2 function (Review).Molecular medicine reports · 2019Review
- The Horizon of a Therapy for Rare Genetic Diseases: A "Druggable" Future for Fibrodysplasia Ossificans Progressiva.International journal of molecular sciences · 2018Review
- MicroRNA-365 regulates IL-1β-induced catabolic factor expression by targeting HIF-2α in primary chondrocytes.Scientific reports · 2017Article
- Effects of miR-146a on the osteogenesis of adipose-derived mesenchymal stem cells and bone regeneration.Scientific reports · 2017Article
- Towards a cure for Fibrodysplasia ossificans progressiva.Annals of translational medicine · 2016Article
- Signaling Receptors for TGF-β Family Members.Cold Spring Harbor perspectives in biology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe ACVR1/Alk-2 gene, encoding a BMP type I receptor, is mutated in Fibrodysplasia Ossificans Progressiva, a severe form of heterotopic ossification. Regulation of ACVR1/Alk-2 expression, still poorly understood, is likely to be controlled by transcriptional and post-transcriptional mechanisms. In our work, we focused on the functional role of the 3'UTR region of the gene and on microRNAs as possible modulators of the ACVR1/Alk-2 expression.
resultsThe ACVR1/Alk-2 3'UTR region consists of a 1.1 kb sequence harboring several putative, well-conserved binding sites for miRNAs in its proximal half, and AU-rich elements in the distal one, as assessed by bioinformatic analysis. The functional role of this region was tested in presence of transcription inhibitors and in transfection experiments in different cell lines, with a ACVR1/Alk-2-3'UTR reporter construct. By this transfection-based approach, we have also verified that three microRNAs, among those predicted to target ACVR1/Alk-2 gene by in silico analysis, can bind its 3'UTR sequence thereby modulating its expression.
conclusionIn this work we demonstrated that the ACVR1/Alk-2 transcript is unstable in presence of inhibitors of transcription. Functional analysis of the 3'UTR region by Luciferase reporter assays showed that it plays an inhibitory role on ACVR1/Alk-2 gene expression. Moreover, we found that specific miRNAs are involved in modulating ACVR1/Alk-2 gene expression as suggested by binding sites prediction in its 3'UTR sequence. In particular, we found that mir148b and mir365 were able to down-regulate ACVR1/Alk-2 expression, whereas mir26a showed a positive effect on its mRNA. Our data contribute to elucidate some of the mechanisms intervening in the modulation of ACVR1/Alk-2 expression. Considering that no specific and effective treatment of FOP is available, clarifying the basic mechanisms of the ACVR1/Alk-2 gene biology may provide means to develop innovative therapeutics approaches.
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